Appendix 1. MRC Centre Principal Investigators 2016

Director Professor Michael Hanna

Co-directors Professor Mary M. Reilly Professor Francesco Muntoni

Co-directors Newcastle Professor Kate Bushby Professor Doug Turnbull

London Dr Chris Clark Professor Giulio Cossu Professor Michael Duchen Professor Elizabeth Fisher Professor Xavier Golay Professor Linda Greensmith Professor John Hardy Professor Henry Houlden Professor Kristjan Jessen Professor Dimitri Kullmann Professor Martin Koltzenburg Dr Michael Lunn Professor Paul Matthews Professor Jennifer Morgan Dr Gita Ramdharry Professor Gipi Schiavo Dr Stephanie Schorge Dr John Thornton Professor Thomas Voit Professor Paul Whiting (as of Oct 2016) Professor Tarek Yousry

Newcastle Professor Andrew Blamire Dr Grainne Gorman Professor Rita Horvath Dr Kieren Hollingsworth Professor Hanns Lochmüller Dr Robert McFarland Dr James Miller Professor Avan Aihie Sayer (as of Aug 2016) Professor Volker Straub Professor Robert Taylor Professor Michael Trenell

Cambridge Professor Patrick Chinnery Senior Team

Professor Michael Hanna

I am interested in how molecular genetic and pathophysiological knowledge can translate into precision diagnostics and treatments in neuromuscular diseases. I established and funded collaborative interdisciplinary clinical, genetic and cellular research programmes in channelopathies, mitochondrial disease and degenerative myopathies that have progressed molecular understanding, resulted in new diagnostic tests and improved patient outcomes in experimental trials. My channel research has translated into the UK national NHS highly specialist clinical service and diagnostic reference laboratory and was selected as a REF 2014 UCL impact case. I am interested in tackling the “translational gap” between discovery and patient benefitThe MRC Centre links UCL and Newcastle universities and provides a national experimental medicine platform. Our translational impact includes stratified patient cohorts >10,000 patients, 99 natural history studies and experimental trials completed, 8000 human cell lines in MRC biobank, 24 clinical and non-clinical PhD students graduated, new MRI biomarkers for NMD adopted internationally, >1000 publications across all PIs, European Medicines Agency orphan drug status & recent, 2015, FDA licensing based on MRC Centre trials.

Added value of being an MRC Centre PI My research has benefitted enormously from the MRC Centre. The support from the trial coordinators has been crucial for the development of patient cohorts, the natural history studies and the clinical trials. Access to the state of the art biobank facilities has facilitated pathogenetic and pre-clinical studies in channelopathies and IBM. The MRI biomarker development in UCL has allowed us to develop a biomarker which is responsive over 1 year in IBM which will be revolutionary in future clinical trials. The training programme of the centre has allowed us to recruit excellent clinical and non-clinical PhD students who have contributed to may of my studies in channelopathy, mitochondrial diseases and IBM.

Professor Mary M. Reilly

2 | P a g e I have a long standing research interest in the inherited neuropathies with an emphasis on translational research. A major part of our current programme is gene identification (e.g. NEFH, BICD2, MARS, FBOX38) and functional analysis of identified genes (e.g. BICD2, FBOX38 and IGHMPB2). My more clinically focused translational research incudes detailed natural history studies in many inherited neuropathies (CMT, HNPP, HMN, HSN, TTR-FAP) with the aim of being trial ready as well as understanding the disease pathogenesis and evolution better, developing new outcomes measures (e.g. CMT neuropathy score for CMT) and new disease biomarkers for disease progression (e.g. MRI neuromuscular protocol for CMT1A). I was the UK PI for the first international UK-Italian trial in CMT1A and currently am conducting a pre-clinical trial outcome measure identification study in HSN1 in preparation for a clinical trial of serine in HSN1 based on work of our group and others in the pathogenesis of this condition and an aerobic exercise trial in CMT1A.

Added value of being an MRC Centre PI My group has had major benefit from the MRC Centre. The support from the experimental medicine trial coordinators has allowed us to setup and develop the MRC Centre inherited neuropathy stratified cohort which currently has 3668 patients entered. The use of this cohort and also fibroblasts from the MRC Centre biobank has been instrumental in helping both new gene discovery and functional studies in these new genes. The experimental medicine trial coordinators have also helped the setting up of and the coordination of the ongoing aerobic exercise study in CMT. The MRI biomarker development in UCL has allowed us to develop a biomarker which is responsive over 1 year in CMT1A which will be revolutionary in future clinical trials. The training programme of the centre has allowed us to recruit excellent clinical and non-clinical PhD students who are the first authors in many of our studies and publication.

Professor Francesco Muntoni

I am a paediatric neurologist clinician scientists interested in clinical and molecular aspects of paediatric neuromuscular disorders, and responsible for a national clinical and diagnostic service for rare congenital muscle diseases. I have been co-director of the MRC Centre since its inception. Regarding my research interests, I am actively involved in the deep phenotyping of children with neuromuscular diseases which led to the identification of more than 30 neuromuscular disease genes, 8 of which by my group. I have pursued functional characterisation of some of these genes by relevant knock-in or knock down animal models.

I have a strong translational research interest in Duchenne muscular dystrophy (DMD) and spinal muscular atrophy. I am the Principal Clinical Investigator of an UK Consortium established a decade ago to pursue genetic therapies for Duchenne muscular dystrophy (DMD), and spinal muscular atrophy (SMA) using splice switching antisense oligonucleotides. I performed 3 investigator led clinical trials to induce exon skipping in DMD using antisense oligonucleotides (targeting exon 51, and exon 53 using a morpholino chemistry, see http://www.skip-nmd.eu/).

Added value of being an MRC Centre PI The MRC Centre allows me to: i. have study coordinators support for the clinical trials and natural history studies currently underway in the Dubowitz Neuromuscular Centre (more than 20 at the moment); ii. access state of the art biobank facilities to assess the identification of novel targets for

3 | P a g e antisense oligonucleotides and other approaches relevant for a variety of neuromuscular diseases; iii. develop novel non-invasive muscle imaging; iv. access animal facilities for testing efficacy of novel therapeutic approaches; v. Train the next generation of clinician scientists with expertise in experimental trials in children

Professor Kate Bushby

Kate Bushby is a clinical academic with joint appointments between the John Walton Muscular Dystrophy Research Centre at Newcastle University and the NHS. She is a member of the Neuromuscular Research Group within the Institute of Genetic Medicine at Newcastle University and plays a leading role in the National Commissioning Group (NCG) for rare neuromuscular diseases. Along with Volker Straub, Professor Bushby was one of the founding coordinators the TREAT-NMD network for accelerating therapy development in neuromuscular diseases. She now plays a leading role in the European and national rare disease policy areas, and is acting as an invited expert on the new Commission expert group on rare diseases. In addition to this, she has overall responsibility for activities relating to the impact of FP7 project RD-Connect on the broader rare disease field. Professor Bushby has a longstanding interest in the molecular of the limb-girdle muscular dystrophies and related disorders and is interested in the best possible development and implementation of care guidelines as well as clinical trials. Her team has developed an extensive programme of research in NMD from basic molecular pathology to clinical studies.

Added value of being an MRC Centre PI My research has benefitted in multiple ways from the MRC Centre. The support from the trial coordinators, the access to a biobank and the PhD students have all contributed to my research in muscular dystrophies. The interaction between PIs in Newcastle and UCL through the MRC centre has had major benefits to the Newcastle Neuromuscular disease research programme.

Professor Sir Doug Turnbull

Professor Sir Doug Turnbull is Director and PI of the MRC/BBSRC Centre for Ageing and Vitality focused on mechanisms of ageing and how these are modified by lifestyle interventions. The MRC/BBSRC Centre was renewed in 2013 and predominantly explores the role of mitochondria in

4 | P a g e ageing and age related disease. Professor Turnbull is also Director of the Centre for Mitochondrial Research, which has had a major impact on mitochondrial disease over the last four years. Professor Turnbull also had a major role in changing the law to allow mitochondrial donation in the UK, working closely with policy makers and patients. Professor Turnbull led the commissioning of a new and unique NHS service for patients with mitochondrial disease – the NHS Highly Specialised Service for Rare Mitochondrial Diseases of Adults and Children. Coordinating activity across three UK centres (Newcastle, London and Oxford), this NHS service provides optimal care for patients and provides an outlet for the clinical research undertaken at MRC Centre for Neuromuscular Diseases.

Added value of being an MRC Centre PI Being a centre PI gives unique ability to develop long term cohorts and then translate the findings from this research into improved healthcare. Being on two sites allows unrivalled access to expertise in neuromuscular disease across two sites.

London

Professor Linda Greensmith

Our group uses a range of techniques and animal and cellular models, to examine the underlying pathomechanisms of neuromuscular disorders that affect motor neurons and muscles, including ALS, dHMN and IBM. We have extensive experience of undertaking preclinical studies of novel agents in mouse models of neuromuscular disease and have a longstanding interest in the therapeutic potential of chaperones for mis-folding disorders. We have shown that a novel co-inducer of protein chaperones called arimoclomol, ameliorates disease in models of ALS and IBM. These results have resulted in clinical trials in both ALS and IBM patients. We are also developing a novel approach to restore function to paralysed muscles using stem cell-derived grafts of motor neurons that express channelrhodopsin-2, a molecular photo-sensor, to establish functional neuromuscular junctions with denervated muscles.

Added value of being an MRC Centre PI The added value of being an MRC Centre PI include access to outstanding clinical and basic PhD students, access to the neuromuscular biobank, opportunities to deliver translational studies in patients in investigator led clinical trials.

5 | P a g e Dr Chris Clark

My research focus is on the development and application of diffusion tensor imaging (DTI) and tractography for the understanding of neurological disability. Tractography uniquely allows the mapping of the white matter tracts of the living human brain. These methods can be used to reconstruct a wide range of clinically eloquent tracts such as the cortico-spinal tracts, fornix, optic radiations and uncinate fasciculus among others. A particular theme of research in which I have been active is the development of these methods for the purposes of neurosurgical planning in both children and adults. I am also using these methods to investigate the relationship between white matter damage and post-surgical deficits. I am leading a number of research projects both on the development of tractography methods, using for example Markov Chain Monte Carlo methods, as well as a wide range of clinical studies in children focused on (temporal lobe epilepsy, febrile convulsions, infantile spasm) and brain tumour diagnosis and collaborate with colleagues on studies in developmental amnesia. I am also actively participating in adult studies of stroke recovery and early white matter damage in familial Alzheimer’s disease.

Added value of being an MRC Centre PI Membership of the MRC consortium has allowed the development of a programme of research in imaging muscle in children at Great Ormond Street Hospital in particular diffusion MRI techniques. Access to collaborators across the consortium has strengthened this work including important interactions with the adult imaging team at Queen Square.

Professor Giulio Cossu

Giulio Cossu (GC) is recognized for his pioneering work on skeletal myogenesis and for the first cell therapy trial with stem cells for muscular dystrophy. He originally showed that neural tube (Vivarelli and Cossu, Dev. Biol. 1986) and, subsequently, dorsal ectoderm (Cossu et al., Development 1996) activate, through different Wnts, distinct myogenic programs in epaxial and hypaxial somitic progenitors, a notion now in developmental biology textbooks. He also pioneered studies on myogenic cell heterogeneity (Cossu and Molinaro, Curr. Topics Dev. Biol. 1987) by showing intrinsic differences among embryonic, foetal and adult myogenic progenitors (Biressi et al. Dev. Biol. 2007) whose molecular basis he recently elucidated (Messina et al. Cell 2010): these studies outlined an unforeseen parallelism with the hematopoietic system, supporting the idea that at least some

6 | P a g e tissues of developing mammals are built in subsequent stages by different families of progenitors. In collaboration with M. Buckingham laboratory, Giulio elucidated the hierarchy of the different myogenic regulatory factors (Tajbakhsh et al. Cell 2007) and also identified unexpected expression of one of these factors, Myf5 in non-somitic progenitors such as the neuroectoderm (Tajbakhsh et al. Neuron 1994) and the lateral mesoderm (Salvatori et al. J. Cell Sci. 2005). These observations led to the identification of a bone-marrow derived, circulating myogenic progenitor cell in adult mice (Ferrari et al. Science 1998) whose embryonic precursors were later identified in the dorsal aorta (De Angelis et al. J Cell Biol. 1999). These cells, named mesoangioblasts, are able to proliferate in vitro and contribute to mesoderm tissues upon transplantation (Minasi et al. 2002). Mesoangioblasts were used for the first successful cell therapy protocols of muscular dystrophy in mice and dogs (Sampaolesi et al. Science 2003; Nature, 2006). After characterization of human mesoangioblasts as a subset of muscle pericytes (Dellavalle et al. Nature Cell Biol. 2007) whose lineage was traced in mice (Dellavalle et al. Nature Comm. 2011), these cells were used by GC for a “first in man” phase I/II clinical trial based upon allo-transplantation of donor mesoangioblasts from an HLA- identical donor in patients affected by Duchenne muscular dystrophy (Cossu et al. EMBO Mol. Med. 2015). Ongoing research focuses on the optimisation of the transplantation protocol and on the development of different gene correction strategies including cell mediated exon skipping (De Angelis et al. PNAS 2002) and development of Human Artificial Chromosomes encoding the dystrophin locus (Tedesco et al. Sci. Transl. Med. 2011). Recently he was awarded a Wellcome Trust HICF grant to conduct a “first in man” cell therapy phase I/IIa trial of cell-mediated for DMD.

Giulio is author of more than 200 peer-reviewed publications (H index: 60); he has been invited as speaker in most meetings on myogenesis and stem cells and has organized EMBO workshops and Gordon Conferences on this topic. He receives funding from many national and international agencies, such as BHF, WT, MRC, Telethon, Duchenne Parent Project, Human Frontiers Science Organization, European Community, European Research Council and others.

Added value of being an MRC Centre PI Giulio greatly benefits from being a PI of the Centre, since he can interact and collaborate with leading experts in neuro-muscular diseases. For example, the recently funded trial has been designed with Francesco Muntoni and Jennifer Morgan who indeed are co-Is of the trial.

Professor Michael Duchen

We are interested in a wide range of issues related to mitochondrial biology and cell signalling. Much of our current work is focused on interrelationships between calcium signalling, mitochondria and free radicals in cell physiology and pathophysiology. This work embraces questions about the contributions of mitochondrial function to intracellular calcium signalling. We are fascinated by the intimate dialogue between mitochondrial biology and cell signalling systems. How do cell signalling pathways impact on and regulate mitochondrial physiology? How do subtle changes in mitochondrial function affect the physiology of the cell? How are mitochondria in different cell types specialized to match the specialized differentiated function of the cells they inhabit? We are especially concerned to characterise the contributions of

7 | P a g e mitochondrial dysfunction to cell injury and cell death - by necrosis or apoptosis – that takes place in situations such as ischaemia, reperfusion injury and in the neurotoxicity mediated by glutamate or beta-amyloid. Another core theme again involving a complex dialogue is the mitochondrion as both a site and a target of oxidative stress and damage in disease models. Most of our work involves live cell fluorescence microscopy and imaging, including confocal, multiphoton and fast read-out cooled CCD instruments. All approaches have been adapted to allow the simultaneous or near simultaneous measurement of multiple variables - cytosolic calcium and mitochondrial potential, cytosolic calcium and mitochondrial calcium, NADH autofluorescence and cytosolic calcium or cytosolic magnesium and so on. We have a broad general interest in functional cellular imaging and in the development of new approaches to imaging aspects of cell function using targeted probes, GFP tagged , FRET, FLIM and so on. Interests of the lab extend through a wide range of biological problems in which mitochondria are involved - in ischaemia reperfusion injury in the heart, in the role of mitochondrial function in fertility in the mammalian egg (with John Carroll), in mitochondrial function and septic shock syndrome in liver, kidney and muscle, in mitochondrial biogenesis following exercise and training in muscle, and in mitochondrial dysfunction in beta cells in diabetes. This rather unusual breadth has had a positive influence on all our work, as resolving problems in one system invariably seems to illuminate problems with others. We have been astonished at the frequency with which a small number of basic principles are recapitulated in a wide and disparate array of models.

Added value of being an MRC Centre PI Our inclusion in the MRC Centre has brought us an increased interaction with other Centre PIs and an increased involvement in research problems related to neuromuscular disease. Access to the Biobank has allowed us to generate models of a number of neuromuscular diseases which have now become a major focus of much of the work in the lab.

Professor Elizabeth Fisher

My background is in mouse and human molecular genetics, with an emphasis on developing novel mouse models of neurodegenerative disease. I have two main areas of interest within my laboratory: motor neuron diseases and Down syndrome – Alzheimer’s disease. In both areas, my laboratory has produced and characterised – in collaboration with colleagues at UCL, the , MRC Harwell, and elsewhere – new mouse models, such TDP43 and FUS mutants, that have given new insights into disease mechanisms. We are currently interested in the humanisation of the mouse genome, a technically challenging process, to determine if knocking in human sequences can yield more accurate models of neurodegenerative disease. At the same time it is essential to recognise that mice model aspects of disease and we need to take a sophisticated approach to both what we learn from the mouse, and how new insights from clinical, iPSC and other studies can feed back to optimise our mouse models.

Added value of being an MRC Centre PI Being a PI at the MRC Centre for Neuromuscular Disease gives me unparalleled access to colleagues with clinical, basic and translational expertise to phenotype the mice we produce, in depth, and to compare to the human condition. This is facilitated by the Centre.

8 | P a g e Professor Xavier Golay

Professor Golay’s research interests lie at the intersection of many disciplines, such as NMR physics, chemistry, physiology and . They include the development of MRI as a translational tool for neurological diseases, measuring identical image-based biomarkers from mouse to human, and from the laboratory to the clinical settings. As has many meanings, parts of his most important research interests include the development of MRI techniques to be used as image-based outcome measures or biomarkers in the same way in animal model of diseases or in human patients. His hope is to reduce the cycle of drug development in neurological diseases by allowing academic or pharmaceutical institutions to use similar tests across species.

Added value of being an MRC Centre PI Being an MRC Centre PI helped me move into new applications in which MRI could play a central role as an early biomarker of disease change, in particular considering the upcoming possible disease-modifying interventions coming in the field of neuromuscular diseases.

Professor John Hardy

My research interests are in the genetic analysis of disease. Historically, we have worked on the genetic analysis of Alzheimer's disease and other dementias. More recently, we have worked on Parkinson's disease and other movement disorders and, most recently on motor neuron disease. Our early studies were on mendelian forms of disease and these studies continue, but an increasing focus has been on the genetic analysis of complex traits related to disease. Additionally, this latter analysis has made us increasingly interested in population genetics because the risk variants for human traits are likely to be different in different racial groups. In all cases our intention is to develop an understanding of the underlying genetics of a disorder so we can work with those making cellular and animal models of the disease to help, both in the understanding of disease mechanisms and to help in the search for treatments. In this regard, we therefore have three types of collaborations: collaborations with clinicians who treat patients with disease, especially colleagues at the Institute of , but also elsewhere, collaborations with other geneticists to

9 | P a g e collaboratively analyse such patient material, and collaborations with cell biologists and transgenic mice people to enable them to build good models of disease.

Added value of being an MRC Centre PI The MRC Centre has allowed my group to have increased interactions with clinical, basic and translational expertise through the centre PIs and an increased involvement in research problems related to both neuromuscular diseases and neurodegenerative disease including mitochondrial dysfunction.

Professor Henry Houlden

The Neurogenetics laboratory at UCL Institute of Neurology is in a pivotal position, and uniquely situated to direct translational opportunities and advance our understanding of neurological disease. The Neurogenetics team have had the foresight to establish and develop a number of cutting-edge technologies, such as the UCL diagnostic and research next generation sequencing facility, the neurological disease gene analysis pipeline and recently I became national lead for the Neurology and Neurodegeneration England Clinical Interpretation Partnership (GECiP), setup to examine all neurology genomes and contains over 150 scientists and clinicians. My laboratory has been at the forefront of neuromuscular disorders, resulting in the identification of several genes for neuromuscular, spastic paraplegia and motor neuronopathies. Importantly, the identification of disease genes has not only led to diagnostic benefit for many patients and families, but also the discovery of new disease-causing pathways that have led to novel and effective treatments, such as in the identification of two riboflavin transporter genes that cause childhood onset motor neuron disease. My laboratory has a demonstrable history of training early career clinicians and scientists, which is essential in sculpting the future of this field.

Added value of being an MRC Centre PI The MRC Centre has brought considerable added value to my genomics research with; well- characterised neuromuscular cohorts for research for gene discovery, high recruitment of patients to the 100,000 genomes sequencing project, collaboration on clinical and functional aspect of a number of disease genes to advance disease pathway understanding.

10 | P a g e Professor Kristjan Jessen

We are interested in Schwann cells, the glial cells of peripheral nerves. These cells provide signals, which during development are required for neuronal survival, and which are essential for the integrity of peripheral nerves in the adult. They also make myelin-sheaths around axons that are needed for the normal conduction of nerve impulses. In damaged nerves, Schwann cells guide re- growing axons and make nerve repair possible. Schwann cells show a striking ability to de-differentiate. This happens for instance when nerves are injured and it is phenotypic plasticity that generates an environment that supports axon growth and nerve regeneration. But Schwann cell de-differentiation and de-myelination is also a major problem in the common inherited and acquired peripheral neuropathies. The work of the laboratory addresses a group of interlocking issues in Schwann cell biology. (i) Early Schwann cell development and the biology of the Schwann Cell Precursor (ii) Control of myelination (iii) The response of Schwann cells to injury and genetic disease, including the process of de- myelination and control of axon re-growth and nerve repair. To learn about these events, we study molecular signalling in neural crest cells and between neurones and glia, examine how factors control differentiation programmes and analyse intracellular signalling cascades that regulate survival, proliferation, myelination and demyelination. We use cells from rats, and normal and transgenic and knockout mice, and a variety of molecular, biochemical, cell biological and cell culture techniques.

Added value of being an MRC Centre PI Increasingly our work focusses on the third of the issues outlined above, namely the role of Schwann cells in injury and disease. In this context we have benefitted substantially from our links and collaboration with members of the MRC Centre for Neuromuscular Diseases.

Professor Dimitri Kullmann

My research focuses on synaptic transmission and plasticity, and neurological channelopathies affecting the CNS, peripheral nerve or muscle, and gene therapy for neurological diseases. Some of the insights from fundamental synaptic function and channelopathies have been harnessed to develop gene therapy tools that are potentially amenable to clinical translation.

11 | P a g e Added value of being and MRC Centre PI Mutations of ion channels and other synaptic proteins identified through the MRC centre provide unique insights into the causation of a range of diseases characterised by abnormal neuronal, synaptic or muscle function. We have also been able to identify patients with autoimmune disorders affecting neuromuscular function. This has allowed my laboratory to branch out into new directions including molecular dynamics of normal and mutated muscle ion channels, and studying the effects of autoantibodies on synaptic signalling.

Dr Michael Lunn

Dr Michael Lunn was appointed as consultant neurologist in 2005. He has an interest in inflammatory neuropathies and his research has concerned Guillain-Barre syndrome, CIDP and paraproteinaemic neuropathies. He is also clinical lead in neuroimmunology and Coordinating Editor of the Cochrane Neuromuscular Disease Group, now based in the MRC Centre.

Added value of being an MRC Centre PI The MRC Centre provides opportunities for utilising all aspects of the translational research in many areas of neuropathy which can be applied to clinical and inflammatory neuropathies. This cross- interest seeding encourages the development of relevant but novel scientific thought in pathogenic mechanisms, relevant common pathways and outcomes measurement. Patients are included in clinical trials of established unproven or novel therapies from multiple physicians as they can be appropriately triaged by the clinician with the greatest expertise. Outputs from such cross fertilisation have been relevant clinical projects on the usefulness of VEGF in POEMS syndrome diagnosis, a clinical study in a cohort of anti-MAG patients, over 17 publications from the PeriNomS study, four clinical trials and current discussions with three potential new PhD students.

Professor Paul Matthews

Paul Matthews, OBE, MD, DPhil, FRCP, FMedSci is Head of the new Division of Brain Sciences in the Department of Medicine of Imperial College, London. His research is noted for innovative translational applications of clinical imaging for the . This has developed with exploitation of the powerful synergies between the physical and quantitative sciences and medicine. His was the founding Director of two internationally leading research imaging centres, the Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) and,

12 | P a g e later, of GlaxoSmithKline’s Clinical Imaging Centre (now a public “spin out” as Imanova, Ltd). From 2005 - 2014 he was a Vice President, GlaxoSmithKline Medicines Discovery and Development. He is one of the small number of senior clinical academics in the UK with industry experience. Professor Matthews’ research has addressed related themes. He has extended applications of advanced imaging methods to answer a new range of clinical research questions. He collaborated closely with Oxford colleagues (especially Professor S. Smith) in applications developments for advanced structural and functional brain imaging incorporated into the open access FSL software distributed by the FMRIB Centre, now one of the two most widely used image analysis software “toolboxes” worldwide. While at Imperial and GSK, his group (then including Professor T. Nichols, now at the University of Warwick) piloted approaches extending these methods for the first properly controlled, prospectively designed imaging genetics studies. Over the last 5 years, he has been Chair of the Imaging Working Group for UK Biobank, which is pioneering an ambitious programme for very large population imaging as part of the UK Biobank (Prof Sir Rory Collins, CEO). MRI scanning of the brain, heart and body, along with DEXA and 3D carotid ultrasound, was initiated in a dedicated imaging centre at UK Biobank's Cheadle (Manchester) site in May, 2014. Professor Matthews’ work to develop the underpinning methods has focused on applications in drug development and disease outcomes monitoring. His former, GSK-based, research group harnessed the tools particularly for experimental clinical neuroscience drug development. An area of particular interest in that context involved development of novel methods for monitoring the progression of muscle pathology in Duchenne Muscular Dystrophy. Amongst many external commitments, Professor Matthews has served two terms on the MRC Neuroscience and Mental Health Board and remains active on several committees; is a member of the HEFCE REF Neuroscience Subcommittee for assessment of Neurosciences, Psychology and related areas; and is a member of the Steering Committee for the UK Dementias Platform. Professor Matthews was awarded an OBE in 2008 for services to neuroscience. He was elected to the Academy of Medical Sciences in 2014 and to the Academea Europea in 2015.

Added value of being an MRC Centre PI Association with the Centre has allowed him to continue collaborations for imaging of muscle pathology, an area of immediate new therapeutic potential.

Professor Jennifer Morgan

Research Summary The overall objectives of my research programme are to: • Define the most useful stem cell populations for reconstitution of skeletal muscle. • Determine factors that control muscle stem cell properties. • Investigate the muscle regenerative capabilities of stem cells other than satellite cells. The ultimate aim of my research programme is to move stem cell therapies for muscular dystrophies into the clinical arena.

Added value of being an MRC Centre PI

13 | P a g e The added value of being an MRC PI is the translational intellectual environment which focusses on translating research findings rapidly into patient benefit. The biobank is an invaluable resource of cells and material for my research programme.

Dr Gita Ramdharry

Dr Ramdharry is an Associate Professor of Rehabilitation Sciences and a Neuromuscular Specialist physiotherapist. She splits her time between the Faculty of Health, Social Care and Education at Kingston University/St George's , and the MRC Centre for Neuromuscular Diseases. At the centre she leads the Neuromuscular Rehabilitation Research Team and has been the recipient of an NIHR Clinical Lectureship and NIHR Research for Patient Benefit project grant, in addition to other chartable and HEI awards. Her team conducts studies of exercise, falls interventions, functional outcome measurement and orthotics with the overall aim of helping people with neuromuscular diseases to live well with their condition. Dr Ramdharry also works clinically as a physiotherapist at the centre.

Added value of being an MRC Centre PI The MRC Centre for Neuromuscular Diseases is unique in that the research conducted by the PIs spans the bench to beyond the bedside and into the community where people participate in society. I am proud that the work of my team extends to people's daily lives, and the opportunities to engage and collaborate with my colleagues at the centre ensure a deep understanding of the pathophysiology and impact of these diseases. Our approaches to improve physical functioning are underpinned by this science.

Professor Gipi Schiavo

My research programme has provided major contributions to infection biology and cellular neurobiology by elucidating the mechanism of action of several bacterial toxins, which has been crucial for their exploitation as specific tools in cell biology and the optimisation of recombinant vaccines; and more recently by revealing key steps in the regulation of the axonal retrograde transport of ligand receptor complexes, such as neurotrophins and their receptors in neurons.

14 | P a g e In particular, we elucidated the role of Rab7, a small GTPase regulating the maturation of endosomal organelles, in the axonal retrograde transport of signalling endosomes, and BICD1 in the sorting and homeostatic control of neurotrophin receptors on the plasma membrane. My current research programme aims to elucidate the crucial role played by deficits in axonal transport in neurodegeneration and it is now targeted to the identification of novel molecules restoring physiological rates of axonal transport in disease conditions.

Added value of being an MRC Centre PI Being a MRC Centre PI allows me an increased connectivity with likely minded investigators focussed on elucidating the mechanism of key neuromuscular diseases at molecular, cellular and organismic level and discovering new therapeutic interventions for the patient’s benefit.

Dr Stephanie Schorge

We are interested in how ion channels alter neurological disorders (such as epilepsy and ataxias) and also how neurological disorders alter ion channels. In particular we are interested in how in ion channels changes their behaviour, and how changes caused by splicing may lead to changes in the course and treatment of diseases. Voltage-gated ion channels are often subject to extensive alternative splicing and the functional and neurological impact of changes in this splicing, as well as the factors regulating it are currently largely unknown. In the lab we regularly record from sodium, potassium, calcium and chloride channels. A close collaboration with the Experimental epilepsy group at IoN involved developing viral-mediated expression to permit heterologous expression of ion channels in difficult to transfect cells, and a close collaboration with the MRC-funded Neuromuscular Centre at IoN means we have a regular stream of novel mutations identified in patients to investigate as well as normally occurring splice variants. We have experimented with a variety of model systems, from oocytes to differentiated teratoma cells, and are constantly looking for ways to better reproduce the cellular environments that are relevant for the changes in ion channel behaviour. Stephanie Schorge is funded by a fellowship endowed by the Worshipful Company of Pewterers.

Added value of being an MRC Centre PI We work on ion channels in the CNS and in muscles, but in many cases the phenotype and variability of muscle channels that we obtain from our colleagues in the MRC Neuromuscular centre, are much more detailed than information about CNS diseases, so our collaboration with the MRC centre not only gives us tremendous insight into how mutations change muscle channels, but gives us a step ahead for understanding variability in channels in general.

15 | P a g e Dr John Thornton

John Thornton is Reader in Clinical MRI Physics at the UCL Institute of Neurology, and Consultant Clinical Scientist and Head of Clinical MRI Physics at the National Hospital for Neurology and Neurosurgery, Queen Square, London. My group’s research aims to benefit patients in the short term by delivering innovative MRI methods into our hospital neuroradiology service to improve patient diagnosis, treatment and management, and in the longer term by establishing validated imaging outcome measures to enable trials of important new experimental therapies. Key themes are advancing MRI Safety, particularly for patients implanted with intracranial electrodes, advanced MRI methods for neurosurgical guidance, and MRI outcome measure methods for neuromuscular diseases and neurodegenerative conditions. Through the BRC Neuroimaging Initiative we are developing harmonized clinical MRI protocols optimised for diagnosis and research analysis, and through the UCL Centre for Medical Computing / NHNN Neuroradiology collaborative Quantitative Neuroradiology Initiative we will embed validated quantitative imaging disease markers into the Neuro-radiology reporting workflow.

Added value of being an MRC Centre PI The infrastructure, funded through the MRC Centre, including the Centre-funded MRI physicist, has enabled us in London to establish and technically optimize and a number of key muscle MRI outcome measures. Collaborative studies with Centre clinical PIs have provided validation in a number of important patient studies, and cross-Centre interactions between imaging specialists in Newcastle and London have leading to a number of fruitful collaborative activities.

Professor Tarek Yousry

Professor Tarek Yousry is the Head of the Lysholm Department of Neuroradiology (NHNN), Head of the Neuroradiological Academic Unit, Head of the Division of Neuroradiology and Neurophysics (UCL IoN), Director of the MSc in Advanced Neuroimaging and Director of Quality and Safety at the Clinical Research Centre, UCLH. Supported by 9 active grants and documented by more than 240 papers, his translational research focuses on furthering our understanding of disease mechanisms and on establishing outcome measures to be used in clinical trials. He has been the PI for imaging of the MRC Centre for Neuromuscular disease since its establishment (2008-12; 2013-2018). Jointly with Dr John Thornton, Prof Yousry leads the UCL Neuromuscular MRI research group. A major focus of this group is the development of MRI of muscle fat infiltration (degeneration and denervation) as a biomarker both to stratify disease and also to monitor disease progression. The group has shown that the protocol they developed can detect disease progression over a year in

16 | P a g e IBM and even in CMT1A, the most slowly progressive neuromuscular disease (Lancet Neurology, 2016). This work underlines the high responsiveness of MR outcome measures over conventional functional measures, thereby highlighting its potential value in clinical trials. Prof Yousry, together with Dr Thornton and Prof S Ourselin, has established the “Quantitative Neuroradiological Initiative”, to translate quantitative MR into clinical practice. This will enable simple & accurate reporting of disease status and disease progression in neuromuscular diseases. Furthermore, the neuromuscular imaging groups of 3 institutions (UCL IoN, led by Prof Yousry and Dr Thornton; UCL ICH, led by Prof Muntoni; Newcastle University, led by Prof Straub) collaborate to harmonise clinical neuromuscular MR imaging across 3 NHS trusts (UCLH, GOSH, NCL) thereby improving patient management and care.

Added value of being an MRC Centre PI The MRC Centre for neuromuscular disease was instrumental to the development of the UCL Neuromuscular MRI research group, enabling it to leading the field in the development of MR outcome measures in neuromuscular disease.

Professor Martin Koltzenburg

Despite significant advances in our understanding of the neurobiology of nociception, pain continues to be a leading health problem and a significant area of unmet clinical need for novel analgesic drugs. Recent epidemiological surveys have revealed an overall prevalence of chronic pain of up to 20% in the general population. Many of these pains are the symptoms of trivial, self- limiting conditions, but there remains a large number of individuals suffering unrelenting severe pain. Careful clinical studies have identified an abnormal sensitivity of primary sensory neurons as a major culprit in acute and chronic pain states. As a consequence much research in the unit aims to understand the mechanisms determining the normal and abnormal excitability of nociceptors. Translating the insights from laboratory investigations into human research projects we also investigate the psychophysical consequences of an abnormally increased nociceptor activity. Pain is also a clinical problem in childhood and prematurely born babies. Our work in animals has shown that the peripheral nociceptive nervous system starts to develop at a stage that corresponds to week 6 of human pregnancy and its maturation continues well into the postnatal period

Added value of being an MRC Centre PI The MRC Centre has allowed my group to have increased interactions with clinical, basic and translational expertise through the centre PIs which has enhanced my research into painful neuropathies. The centre has also given me the opportunity to supervise an excellent PhD student who is now a post doc in Oxford developing IPS cells to study sensory neuropathies.

17 | P a g e Professor Thomas Voit

My research is focussed on the development of new treatment approaches, notably gene therapy, for neuromuscular disorders (NMDs). It comprises the invention and conception of new molecular treatment approaches and their development as well as the development of new outcome measures (biomarkers, MRI/MRS, muscle force and function measures) and their validation in phase 1-2 clinical trials. Sixteen patents document inventions and publications bearing on the first three drugs under FDA filing for Duchenne MD (ataluren, drisapersen, catena) provide proof of pull-through capacity. My experimental focus will develop new antisense-mediated, Gapmer-mediated, and rAAV-mediated approaches for facioscapulohumeral MD and other MDs such as Becker MD. Functional in vitro and in vivo these approaches will be taken through preclinical and clinical development. I am also interested in muscle homeostasis and therapeutic approaches looking into small molecules, and their combinatorial application together with gene therapy. One focus is the combinatorial approach of antisense and gene therapy for dystrophic tissue. This approach has the capacity to augment the effect of gene therapy in mdx mice 10-fold. These and other new molecular treatment technologies will serve as platform technologies to tackle a large number of NMDs including spinal muscular atrophy, SOD1-linked ALS and Duchenne, Becker, and limb girdle muscular dystrophies.

Added value of being an MRC Centre PI Developing new molecular treatment approaches is critically dependent on primary materials (cells including muscle biopsies, myoblasts and iPS cells), on well-defined patient cohorts in order to design appropriate clinical trials and evaluate endpoints, and on scientific exchange and academic collaboration. The MRC Centre for Neuromuscular Diseases represents an optimal academic and clinical environment for my research and was indeed a major reason for me to join UCL in October 2015. Active collaborations have already started with several MRC PIs (Hanna, Muntoni, Morgan). Currently 272 publications in PubMed, H-Factor 65, > 15000 citations

Newcastle

Professor Andrew Blamire

18 | P a g e My personal research programmes revolve around developing and applying novel Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) methodology as diagnostic and prognostic values and as outcome measures in interventional trials. Neuromuscular imaging: My research group are involved in a wide range of studies developing and applying MR methods for neuromuscular applications. I coordinate the FP7 funded BIOIMAGE-NMD programme and my group is developing diffusion sensitive MRI methods based on the stimulated echo method (STE- DWI) as a probe of tissue microenvironment. The objective of this work is to quantify changes in muscle fibre size distribution which is a feature of tissue degeneration and regeneration in muscular dystrophy. We aim to develop STE-DWI as a tool to measure muscle decline and response to intervention in patients with Duchenne Muscular Dystrophy (DMD). A second method development project funded through MRC Confidence in Concept is looking at how MRI can be used to image neuromuscular motor unit activity as a non-invasive alternative to needle based EMG measurements. With funding from Horizon2020, within the VISION-DMD programme we are establishing the imaging protocol for a major international clinical trial of VBP15, an innovative steroid-like intervention for Duchenne Muscular Dystrophy and will be the central imaging analysis facility for this trial. My group also provides leadership to the imaging study component of the JAIN foundation Clinical Outcome Study in dysferlinopathy and we are one of two analysis centres for this study. Neuroimaging – Dementia: Recent studies using quantitative relaxation imaging (T1 and T2), diffusion tensor imaging, cerebral blood flow imaging (arterial spin labelling) and metabolic measurements by proton MR spectroscopic imaging have revealed different patterns of neurodegeneration between patients with Alzheimer's disease and Dementia with Lewy Bodies. Current work, funded by the Newcastle NIHR BRU in Lewy Body Dementia, is applying MRS spectral editing techniques to examine the role of the excitatory GABA in the symptoms of visual hallucinations which are common in patients with Dementia with Lewy Bodies. Responsive contrast agents for molecular MRI: with funding from EPSRC I am working with Prof David Parker at Durham University to develop a new range of molecular MR contrast agents which are directly imaged by MRI. These new agents are based on the paramagnetic shift between a lanthanide ion and a reporter group within the molecule and have been termed PARASHIFT agents. The agents are designed to be responsive to the tissue environment, providing quantitative readout of physiological parameters such as tissue temperature and pH. Other projects include: Development of 7Li MR imaging in Bipolar Disorder Studies of fatigue and autonomic dysfunction in Sjogren’s Syndrome (Arthritis Research UK funded) including measurement of muscle bioenergetics using 31P-MRS

Added value of being an MRC Centre PI Being a PI on the MRC Centre has allowed me to develop a new theme to my research programme. As a MR physicist with a main interest in novel imaging methodology, historically my focus has been on neuroimaging. Working with the clinical and biomedical colleagues in the Centre has highlighted neuromuscular conditions where imaging could provide more robust diagnostic information and aid our understanding of disease. This has led to new translational projects using preclinical and clinical scanning, opened the way for new collaborations and allowed me to raise the profile of UK imaging research through leadership of major international programmes.

Dr Grainne Gorman

19 | P a g e The aim of my research is to devise and facilitate the prescription of safe and effective exercise protocols into clinical practice which will support people with mitochondrial myopathies to sustain a more physically active lifestyle, whilst targeting the underlying disease mechanisms in a condition, which, currently there are no known cures and few effective treatments. Other major research themes include: Clinical and molecular aspects of mitochondrial disease. Advanced cardiac monitoring to establish the safety and efficacy of exercise in patients with mitochondrial disease. Bringing together our experiences of exercise prescription in developing complex interventions, such as exercise and physical activity, to understand how a physical activity care pathway could be designed and implemented, in collaboration with patients. Evaluation of cognitive changes in patients with mitochondrial myopathies. Development and validation of a patient-centred and disease-specific quality of life tool. Analysis of functional outcome measures that enable us to quantify the impact of symptoms on functional capacity and health related quality of life. Finally another major area of research interest is to explore the emerging role of mitochondrial mechanisms and exercise in age-related loss of muscle mass and strength which begins in the fourth decade of life. This has synonymous associations with increased fragility, loss of functional capacity, loss of independence and increased burden on healthcare costs.

Added value of being an MRC Centre PI The MRC Centre has allowed my group to have increased interactions with clinical, basic and translational expertise through the centre PIs in both Newcastle and UCL. The access to well phenotyped cohorts has enhanced my research in mitochondrial diseases and especially in exercise studies.

Professor Rita Horvath

I was trained as a neurologist at the Semmelweis Medical School in Budapest and started my career as a Clinical Research Fellow of the Hungarian Academy of Sciences. I received funding from the Soros Foundation to do research in mitochondrial diseases with Professor Eric Shoubridge in the Montreal Neurological Institute, which determined the direction of my career ever since. After my return to Budapest, I introduced genetic testing for mitochondrial disease in Hungary, completed my PhD on mitochondrial disease and became a consultant in neurology. In 2000-2007 my research was based on a diagnostic service in Munich, and I focused on identifying the primary cause in a high number of patients with different types of mitochondrial disease. I moved to Newcastle in 2007 and I focussed my research to study diseases caused by abnormal mitochondrial protein synthesis. I have received a New Investigator Award from the MRC and a Consolidator Grant from the ERC for studying a unique mitochondrial condition, reversible infantile cytochrome c oxidase (COX) deficiency and for unveiling factors that are important in the tissue specificity of mitochondrial diseases. I believe that the better understanding of the compensatory factors will offer important clues towards molecular therapies. As a Wellcome Trust Investigator I explore the pathomechanism of nuclear disease genes causing abnormal mitochondrial protein synthesis by using human cells and zebrafish as disease models. In addition to my work on mitochondrial disease, I have developed a new clinical service in Newcastle for a large group of patients with inherited peripheral neuropathies (Charcot-Marie-Tooth disease, CMT).

20 | P a g e The better characterisation of the clinical phenotypes, the improvement of next generation sequencing techniques enabled the identification of the primary genetic cause in a much higher number of patients with CMT. This patient cohort is the base for expanding my research activities in inherited neuropathies and I successfully obtained funding for this research from the Wellcome Trust and from the MRC UK.

Added value of being an MRC Centre PI As an MRC Centre PI, I received extensive help from Professor Mary Reilly (UCL) to develop a new clinic and research programme in Newcastle on Charcot-Marie-Tooth disease. This work is supported with a clinical research fellow, who is currently completing her PhD on CMT. CMT had been identified as an area for research of importance to the MRC neuromuscular centre to be developed and to be linked in with other activities of the centre.

Dr Kieren Hollingsworth

Reducing the cost and patient burden of MRI in clinical trials: acceleration of quantitative MRI using novel reconstruction techniques. MRI is not just a powerful tool for radiologists to visualise diseased tissue, but rather it can be used to accurately measure the disease state of tissue or the function of an organ, and this has informed my research over the last decade. Applications include tracking disease progression in muscular dystrophy, or examining the lipid content of the liver and pancreas and type 2 diabetes. However, MRI examinations typically require the patient to lie still for many minutes at a time, and a whole examination can take an hour or more. This is a lot for a patient to tolerate within the context of other visits in a clinical trial protocol and MRI scanning time is costly (~£500/hr in the UK). There are now active trials in Duchenne muscular dystrophy, a muscle wasting disease that affects young boys as young as 4-5 years old, who find it particularly challenging to keep still in the scanner. My research as Principal Investigator, funded by the MRC, is to develop and validate highly accelerated MRI measurements by acquiring less data and using a new reconstruction technique. To date, I have demonstrated that we can speed up the scanning by a factor of 5 times to measure the progressing disease in muscular dystrophy. The clinical validation work was published in the leading international journal Radiology, available here. The technical exploration of how to find the most robust method for doing this was published in Magnetic Resonance in Medicine and is available here. My present activity as part of this grant is to validate similar accelerations in the heart, and in the liver and pancreas of patients with type 2 diabetes.

Added value of being an MRC Centre PI Being a PI within the MRC Centre for Neuromuscular Diseases has been invaluable in my work for providing close contact between the MR and clinical specialists working within the Centre. In particular, the MRI resource and personnel supported by the centre has ensured that multi-centre research in DMD, LGMD2I and myotonic dystrophy can be executed in a unified way which allows the researchers in the centre to benefit from recruitment in both Newcastle and London.

21 | P a g e Professor Hanns Lochmüller

I have a long-standing interest in the molecular genetics of the inherited myopathies and neuromuscular junction disorders, and my research focuses on the further study of animal models of these disorders as a means to understand their pathophysiology, as well as to develop the means to monitor disease progression and therapeutic interventions. My research encompasses multiple model systems such as zebrafish and mouse in vivo models, cell culture models and clinical studies involving patients. Recent research successes include identifying novel genes for congenital myasthenic syndromes (Senderek et al., 2011; Beeson et al., 2006), developing methods for iPSC cell generation (Dick et al., 2010) and viral vector testing (Jorgensen et al., 2009), and evaluating the effects of potential therapies in vivo (Jorgensen et al., 2011). This has enabled me to secure several prestigious grants including three MRC project grants (one as principal applicant), charitable funding such as AFM and Lundbeck Foundation grants and significant EU funding for networking activities such as TREAT-NMD, BIO-NMD and CARE-NMD. Recent examples of our translational activities include clinical trials of anti-sense oligonucleotides to induce exon skipping in DMD (as part of the MDEX consortium in collaboration with AVI and also working with Prosensa/GSK). I am the local PI for a multi-centre clinical trial of Olesoxime in SMA (in collaboration with Trophos). We are also involved in a long term study of steroid efficacy in DMD funded by NIH. This is in addition to the enabling activities of TREAT-NMD, BIO-NMD, CNMD and EuroBioBank which provide infrastructure (patient registries, BioBanks and materials) to the wider community. These activities continue to contribute to the global translational effort in neuromuscular diseases and have made possible a large number of trials in the UK and abroad. In addition, the model provided by TREAT- NMD is being adopted as an exemplar for the organization of translational activities in rare disorders in general.

Added value of being an MRC Centre PI The MRC Centre has allowed me to draw on the expertise of colleagues in Newcastle and London and work with those colleagues to build a national resource in Genetic disease - this has developed me as an investigator and broadening my network of potential collaborators.

Dr Robert McFarland

In 2000 I began my research career studying the molecular consequences and associated clinical phenotypes of mitochondrial tRNA point mutations. Since then my research has included the

22 | P a g e identification of mitochondrial and nuclear gene defects causing disease in children, factors determining pathogenicity of mitochondrial DNA mutations and clinical research. The latter has specifically involved the development of clinical assessment tools (NMDAS and NPMDS), drug trials and more recently, bringing together a living cohort of almost 1400 individuals with confirmed mitochondrial disease. Research Interests: My research aims are to understand the pathological processes that cause mitochondrial disease in children, explore the molecular aetiology of these diseases and dissect out the factors that influence disease expression. A related research theme is exploration of the natural history of mitochondrial disease, an area that has been greatly facilitated by the development of the multi-centre MRC Mitochondrial Disease Patient Cohort Study (UK) on which I have taken a national lead. The Cohort is also proving a valuable resource for recruitment to clinical trials, another area in which I have a keen interest. Added value of being an MRC Centre PI The MRC Centre has allowed me to draw on the expertise of colleagues in Newcastle and London and work with those colleagues to build a national resource in the form of the MitoCohort - this has developed me as a researcher and broadening my network of potential collaborators.

Professor Volker Straub

Volker Straub is The Harold Macmillan Professor of Medicine and Professor of Neuromuscular Genetics at the Institute of Genetic Medicine at Newcastle University, . He is a director of the university’s John Walton Muscular Dystrophy Research Centre and holds honorary clinical appointments with the Newcastle upon Tyne Hospitals NHS Foundation Trust and the North Tees and Hartlepool NHS Foundation Trust. He is part of the steering committee of the MRC Centre for neuromuscular diseases and an executive board member of the World Muscle Society. He was founding joint coordinator of TREAT-NMD, which has as its ultimate goal accelerating the development of curative treatments for patients with neuromuscular diseases. Professor Straub trained as a paediatric neurologist at the University of Düsseldorf and the University of Essen in Germany. He wrote his PhD thesis on Duchenne muscular dystrophy and worked as a postdoctoral research fellow at the Howard Hughes Medical Centre at the University of Iowa, USA. Within the John Walton Muscular Dystrophy Research Centre Professor Straub has a long-standing interest in the pathogenesis of muscular dystrophies, with research using zebrafish and mouse models. His current research also involves the application of next generation sequencing and other – technologies for the characterization of primary muscle diseases. He is a steering group member of several EU funded projects and is coordinating the FP7 funded EU project SCOPE- NMD. Professor Straub also chairs the MYO-MRI COST-Action (BM1304) studying the applications of MR imaging and spectroscopy techniques in neuromuscular disease. Prof Straub’s academic focus has been and remains translational research for genetic neuromuscular diseases. This research is motivated by his hopes of accelerating the development of curative treatments and enabling the best care for patients.

Added value of being an MRC Centre PI The MRC Centre has facilitated Prof Straub’s work by providing him with a mechanism to draw on the expertise of colleagues in Newcastle and London whilst concurrently working with those

23 | P a g e colleagues to build a national resource for genetic disease. These activities have developed him as an investigator and have broadened his network of potential collaborators

Professor Robert Taylor

I began my research by studying the biochemical and molecular genetic basis of mitochondrial respiratory chain and fatty acid oxidation disorders, with a particular emphasis on understanding the control of oxidative phosphorylation on fatty acid β-oxidation flux. Following periods of post-doctoral research focussed on investigating the role of mitochondrial DNA mutations in diabetes and the development of experimental gene therapy strategies for the treatment of heteroplasmic mitochondrial DNA disorders, I developed a programme of work embedded within a multidisciplinary, NHS Mitochondrial Diagnostic laboratory to both identify and characterise novel mitochondrial and nuclear genetic defects causing mitochondrial disease and dissect the molecular mechanisms leading to cellular dysfunction. The overall aim of my research is to use biochemical, molecular genetic and cell biological tools to diagnose and characterise the molecular pathology associated with human mitochondrial (both mtDNA-derived and Mendelian) disorders so as to understand disease mechanism and benefit patient care through the development of treatments and provision of accurate genetic advice. This work is wide-ranging, encompassing projects aimed at:1. defining the prevalence, natural history and genotype:phenotype correlations associated mitochondrial disease 2. improving the laboratory diagnosis and options for prenatal and preconceptional genetic screening 3. documenting the neuropathological changes associated with mitochondrial genetic disease to delineate the molecular mechanisms leading to neuronal loss and neurological deficits in patients with mitochondrial disease 4. using next generation sequencing strategies including whole exome and whole genome sequencing to identify novel disease genes associated with a range of mitochondrial oxidative phosphorylation defects (focusing primarily on mtDNA depletion syndromes, isolated complex I deficiency and generalised disorders of mitochondrial protein synthesis) with the broader aim of characterising the mechanisms which underlie post-transcriptional mitochondrial .

Added value of being an MRC Centre PI Uniquely positioned at the diagnostic-research interface, I collaborate extensively with a number of International clinical and basic scientists as well as colleagues across the MRC centre, which provides access to unprecedented patient cohorts and the opportunity to study mitochondrial dysfunction in a range of muscle pathologies.

24 | P a g e Professor Michael Trenell

My core research projects look at how metabolism can be improved in a number of different metabolic disorders. A significant focus of my research is on how increased physical activity and exercise can be used as a clinical therapy in metabolic disorders (Type 2 diabetes and non- alcoholic fatty liver disease), neuromuscular disease, ageing and in promoting lifelong health and wellbeing. I also have a strong background in multinuclear magnetic resonance spectroscopy and imaging techniques and use these frequently to investigate metabolism. In January 2009 I established MoveLab under pump priming funding from the Council with clinical colleagues in Newcastle. The objective of this laboratory is to provide a complete translational research platform; building both the evidence base of movement as a clinical therapy and a pathway for delivery into care. At a basic science level, we have a program of studies investigating the interaction of physical inactivity, physical activity, and exercise upon molecular, genetic and metabolic function with collaborators in the UK and overseas. At an intermediate level, we are addressing two key questions: what type of activity is best and how much is needed to use physical activity and exercise as a therapy? These studies are identifying the dose response of both resistance and aerobic exercise upon clinical outcomes. At a clinical delivery level, we are working with clinical care and patient groups to move these findings into clinical care. We are developing the UK’s first accredited professional and patient development pathways for physical activity and exercise for use as a clinical therapy in primary care. This is an exciting area which is expanding rapidly.

Added value of being an MRC Centre PI Being part of the MRC Centre has placed us at the forefront of lifestyle interventions for people with neuromuscular disease. With colleagues in Holland, France and Germany we are helping lead one of the largest trials of lifestyle and self-management for people with neuromuscular disease. The centre has also brought together academics, physicians and AHPs from across multiple sites across the country to better understand the impact of neuromuscular disease on everyday physical activity as well as the potential for everyday movement to be used as a therapy to support patients to self - manage.

Dr James Miller

Local PI for NIHR CSP 23564. UKMyonet. Identification of disease susceptibility genes associated with development and clinical characteristics of primary inflammatory muscle diseases, PM, DM and IBM. Local PI for NIHR CSP 87344. IGOS. Clinical and biological determinants of disease course in Guillain-Barre syndrome: a prospective UK-wide observational study interfacing with the

25 | P a g e International Guillain-Barre syndrome Outcome Study – IGOS. Local PI for NIHR CSP: 131148. RESILIENT. A randomized, double-blind, placebo-controlled, multicenter, parallel group, dose- finding, pivotal, phase IIb/III study to evaluate the efficacy, safety and tolerability of intravenous BYM338 in patients with sporadic inclusion body myositis. Local PI for NIHR ID 13228. Using Next Generation Sequencing to Unravel the Pathogenesis of Sporadic Inclusion Body Myositis (IBM) International - IBM Consortium Genetic Study. This very large collection of DNA will allow more detailed genetic studies to understand the genetic risks factors for this disease.

Added value of being an MRC Centre PI The centre facilitates collaboration with other neuromuscular specialists based in the centre in London.

Cambridge

Professor Patrick Chinnery

Mitochondrial disorders affect approximately 1 in 4300 of the population and cause progressive, incurable diseases that often result in premature death. The primary genetic defect affects either nuclear DNA or mitochondrial DNA (mtDNA), and ultimately leads to a biochemical defect of ATP synthesis. However, despite having the same basic biochemical basis, mitochondrial disorders have an enormously variable clinical presentation and disease course. My laboratory aims to determine the major nuclear and mitochondrial genetic factors that modulate the clinical expression of mitochondrial disorders, thus explaining the variable phenotype. Specifically, we are working to (i) define the sub-cellular mechanism responsible for the mtDNA genetic bottleneck during female germ cell development (ii) characterise novel nuclear gene defects in patients with Mendelian mitochondrial disorders (iii) define critical nuclear-mtDNA interactions through the investigation of homoplasmic mtDNA diseases. These three laboratory research themes dove tail into a clinical translational research programme studying the natural history of mitochondrial disease, and developing new treatments through investigator-led experimental medicine studies and clinical trials in partnership with the pharmaceutical industry.

Added value of being an MRC Centre PI Membership of the MRC Centre for Neuromuscular diseases provides a vehicle for effective collaboration with PIs across the UK, giving access to patient cohorts and technology that increases the pace of translational research in mitochondrial diseases.

26 | P a g e Appendix 2. CVs of new PIs appointed since last review

Thomas Voit

Current role Professor UCL Institute of Child Health and Honorary Consultant, Great Ormond Street Hospital Trust; Director Designate, ICH NIHR Biomedical Research Centre; Vice-Dean for Enterprise, Faculty of Population Health Science

Previous Posts 2006-2015 Professor of Paediatrics (PU-PH), University Pierre et Marie Curie – Sorbonne and Medical and Scientific Director, Institute of Myology, GH Pitie-Salpetriere, Paris, France 2002-2006 Managing Director, Centre for Paediatrics and Adolescent Medicine, University of Essen, Germany 1995-2006 Professor and Chair of Paediatrics and Director of the Department of General Paediatrics and Paediatric Neurology, University of Essen, Germany 1993-1995 Professor of Paediatric Neurology, University of Düsseldorf, Germany

Research profile My research is focussed on the development of new treatment approaches, notably gene therapy, for neuromuscular disorders (NMDs). It comprises the invention and conception of new molecular treatment approaches and their development as well as the development of new outcome measures (biomarkers, MRI/MRS, muscle force and function measures) and their validation in phase 1-2 clinical trials. Sixteen patents document inventions and publications bearing on the first three drugs under FDA filing for Duchenne MD (ataluren, drisapersen, catena) provide proof of pull-through capacity. My experimental focus will develop new antisense-mediated, Gapmer-mediated, and rAAV-mediated approaches for facioscapulohumeral MD. Two patents filed describe the novelty of these complementary approaches silencing the pathologically activated DUX4 at the mRNA and protein level. Functional in vitro and in vivo these approaches will be taken through preclinical and clinical development. A second focus is the combinatorial approach of antisense and gene therapy for dystrophic tissue (patent filed). This approach has the capacity to augment the effect of gene therapy in mdx mice 10-fold. The technologies applied will serve as platform technologies to tackle a large number of NMDs including spinal muscular atrophy (patented, under exploitation), SOD1-linked ALS (patented, under exploitation) and Duchenne muscular dystrophy (patented).

Publications Currently 272 publications in PubMed, H-Factor 65, > 15000 citations

1 | P a g e Giampetro Schiavo

Current role Professor of Cellular Neurobiology, UCL ION

Research profile My discoveries have advanced cellular microbiology and neurobiology by: 1. Elucidating the mechanism of action of bacterial toxins, which has been crucial for their exploitation as vaccines and therapeutics; and 2. Revealing key steps in the regulation of axonal retrograde transport of ligand receptor complexes, such as neurotrophins and their receptors. My research programme at the UCL-Institute of Neurology aims to uncover the molecular mechanisms modulating axonal retrograde transport in health and disease, and identifying new pharmacological targets to restore physiological axonal retrograde transport in neurorodegenerative conditions. I strongly believe that only by understanding the basic principles of membrane trafficking and signalling will we be able to uncover the pathological changes in the nervous system leading to neurodegeneration. These fundamental processes might then be exploited to provide an earlier and more accurate diagnosis and improved pharmacological treatments.

Selected recent publications 1. Rishal I, et al. Motor driven intracellular length sensing in neurons. Cell Rep. 2012 1:1-9. 2. Terenzio M, et al. Bicaudal-D1 regulates the intracellular sorting and signalling of neurotrophin receptors. EMBO J. 2014 33:1582-98. 3. Bercsenyi K, et al. Nidogens are therapeutic targets for the prevention of tetanus. Science. 2014 346:1118-23. 4. Ahmed M, et al. Targeting protein homeostasis as a novel therapeutic approach in Sporadic Inclusion Body Myositis. Sci Transl Med. 2016 8:331ra41. 5. Twelvetrees AE, et al. The dynamic localization of cytoplasmic dynein in neurons is driven by kinesin-1. Neuron. 2016 in press.

Key grants awarded 1. MRC: Novel and bespoke mouse models for dissecting neurodegenerative disease.03/2016 - 02/2020 £1.78M 2. Horserace Betting Levy Board: Why do horses roar? From the beginning to the end of recurrent laryngeal neuropathy. 02/2016 - 01/2018 £100k 3. NC3Rs Fellowship: A new Drosophila-based strategy to study mitochondrial transport and neuronal ageing in vivo. 07/2016 - 06/2019 £200k 4. Wellcome Trust: Control of receptor trafficking as a therapeutic target in the inherited neuropathies (A. Rossor). 07/2016 - 06/2019 £410k 5. MNDA: Regulation of intracellular traffic by TBK1 and its relevance to Amyotrophic Lateral Sclerosis. 09/2016 - 08/2019 £90k 6. Wellcome Trust: The mechanism controlling sorting and axonal retrograde transport in neurons 09/2015 - 08/2020 £1.75M 7. MRC: Investigating deficits of axonal RNA metabolism and axonal signalling in ALS 8. (P. Fratta). 06/2015 - 05/2019 £1.15M 9. Fondation Thierry Latran: Deficits in axonal transport as a target for pharmacological intervention in Amyotrophic Lateral Sclerosis. 09/2015 - 02/2017 €120k 10. Alzheimer’s Research UK: UCL Drug Discovery Institute 09/2014 - 08/2019 £8.8M 11. BBSRC: Mechanisms controlling axonal retrograde transport. 09/2014 - 08/2019 £90k 12. Welcome Trust: Dissecting Neuronal Specificity in Hereditary Neuropathy 06/2014 - 05/2018£250k

2 | P a g e Paul Whiting

Current role Chief Scientific Officer, Alzheimer’s Research UK UCL Drug Discovery Institute

Previous posts 2011 - 2015 Senior Director, Pfizer Neusentis, Cambridge, UK 2010 -2011 Executive Director, Pfizer Regenerative Medicine, Cambridge, UK

Research Biography Paul obtained a first class honours degree in Biochemistry & Microbiology from the University of Leeds, followed by a PhD at the University of London. He moved to the Salk Institute for Biological Studies in San Diego for postdoctoral studies. Paul subsequently joined the Neuroscience Research Centre, Merck Research Laboratories, where he moved from lab scientist to Head of Molecular and Cellular Neurosciences. Paul joined Pfizer in 2006, and in 2008 he helped establish the new Pfizer Regenerative Medicine research unit in Cambridge UK, becoming site head and leading the small molecule and cell therapy programs. In 2011 the regenerative medicine activities were incorporated into a new Pfizer research unit, “Neusentis”, where he was Head of Molecular and Cellular Biology until October 2015 when he moved to UCL Institute of Neurology to become the Chief Scientific Officer for the Alzheimer’s Research UK UCL Drug Discovery Institute. He has extensive experience in Neuroscience drug discovery, from target identification/validation through to leading early stage clinical programmes for both small molecules and cell therapies. He has served on the Medical Research Council Neuroscience and Mental Health Board, and is currently a member of the MRC Regenerative Medicine Research Committee and U.K Regenerative Medicine Platform Board. He served on the Biological Sciences committee for assessment of UK University & Research Institutions (RAE 2008) and the Neuroscience and Psychology committee for assessment of UK University & Research Institutions (REF 2014: Research Excellence Framework). In 2009 he was appointed Honorary Professor in the Division of Biosciences, University College London.

Key Grants awarded Alzheimer’s Research UK. Funding for UCL Drug Discovery Institute. £10M (2015-2020).

Selected Recent Publications 1. Choudhary P, Gutteridge A, Impey E, Storer RI, Owen RM, Whiting PJ, … & Benn CL. (2016). Targeting the cAMP and Transforming Growth Factor-β Pathway Increases Proliferation to Promote Re-Epithelialization of Human Stem Cell-Derived Retinal Pigment Epithelium. Stem Cells Transl Med: 2015-0247. 2. Cao L, McDonnell A, Nitzsche A, Alexandrou A, Saintot PP, Whiting P, … & Stevens EB (2016). Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia. Sci Transl Med: 20; 8 (335). 3. Whiting P, Kerby J, Coffey P, da Cruz L, McKernan R. Progressing a human embryonic stem-cell-based regenerative medicine therapy towards the clinic. (2015). Philos Trans R Soc Lond B Biol Sci. 370 (1680). 4. Choudhary P, Dodsworth BT, Sidders B, Gutteridge A, Michaelides C, Whiting PJ, … & Benn L. (2015). A FOXM1 Dependent Mesenchymal-Epithelial Transition in Retinal Pigment Epithelium Cells. 10 (6). 5. Young GT, Gutteridge A, Fox HD, Wilbrey AL, Cao L, Whiting P, … & Stevens EB (2014). Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research. Mol Ther. 22 (8):1530-43.

3 | P a g e Avan Aihie Sayer

Current role Director, NIHR Newcastle BRC and Professor of Geriatric Medicine, Newcastle University Honorary Consultant in Geriatric Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust Visiting Professor of Geriatric Medicine, MRC Lifecourse Epidemiology Unit, University of Southampton

Research profile Avan Aihie Sayer was appointed Director of the NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Professor of Geriatric Medicine at Newcastle University in January 2016. She led the Newcastle application for the 2016 NIHR Biomedical Research Centre competition. Her research is focused on the role of skeletal muscle in ageing, health and disease particularly the ageing syndromes of sarcopenia and frailty and this has been supported by MRC programme grant funding since 2010.

Recent MRC Programme Grants 1. Sarcopenia and frailty: a lifecourse approach. Sayer AA, Robinson SM, Gale CR, Cooper C. £2,700,000 MRC Programme Grant 2015 – 2020. 2. Sarcopenia, frailty and clinical practice in older people. Sayer AA, Gale CR, Cooper C. £2,840,000 Medical Research Council Programme Grant 2010 - 2015

Selected Recent Publications (PubMed search terms: Sayer AA or Aihie Sayer A or Sayer AP or Aihie A) 1. Sayer AA, Kirkwood TBL. Grip strength and mortality: a biomarker of ageing? Lancet 2015 Jul 18;386(9990):226-7. 2. Nead KT, Li A, Wehner MR, Neupane B et al Contribution of common non-synonymous variants in PCSK1 to body-mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331,175 individuals. Human Molecular Genetics. 2015;24(12):3582-3594. 3. Patel HP, White MC, Westbury L, Syddall HE, Stephens PJ, Clough GF, Cooper C, Sayer AA. Skeletal muscle morphology in sarcopenia defined using the EWGSOP criteria: findings from the Hertfordshire Sarcopenia Study (HSS). BMC Geriatr. 2015 Dec 18;15:171. 4. Roberts HC, Syddall HE, Butchart JW, Stack EL, Cooper C, Sayer AA. The association of grip strength with severity and duration of Parkinson’s: a cross-sectional study. Neurorehabil Neural Repair 2015;29(9):889-896. 5. Dodds R, Sayer AA. Sarcopenia and frailty: new challenges for clinical practice. Clin Med (Lond) 2015; 15 Suppl 6: s88-91. 6. Syddall HE, Westbury LD, Cooper C, Sayer AA. Self-reported walking speed: a useful marker of physical performance among community-dwelling older people? J Am Med Dir Assoc 2015; 16 (4): 323-328. 7. Lewis A, Lee JY, Donaldson AV, Natanek SA, Vaidyanathan S, Man WD, Hopkinson NS, Sayer AA, Patel HP, Cooper C, Syddall H, Polkey MI, Kemp PR. Increased expression of H19/miR-675 is associated with a low fat-free mass index in patients with COPD. J Cach Sarc Mus 2016;7(3):330-344. 8. North TL, Ben-Shlomo Y, Cooper C, Deary IJ, Gallacher J, Kivimaki M, Kumari M, Martin RM, Pattie A, Sayer AA, Starr JM, Wong A, Kuh D, Rodriguez S, Day IN. A study of common Mendelian disease carriers across ageing British cohorts: meta-analyses reveal heterozygosity for alpha 1-antitrypsin deficiency increases respiratory capacity and height. J Med Genet 2016;53(4):280-288.

4 | P a g e Michael Lunn

Current role Consultant Neurologist and Clinical Lead in Neuroimmunology – March 2007 – present National Hospital for Neurology and Neurosurgery, Queen Square, London

Research profile FORCIDP – fingolimod in CIDP CSL Behring funded PATH study - SCIG for CIDP Predictive biomarkers for anti-MAG neuropathy POEMS syndrome – biomarkers and clinical phenotypes Leonard Wolfson Biomarker Discovery Project – biomarker discovery in neurology International GBS Outcomes Study (IGOS) – a cohort study to identify biomarkers in GBS

Selected recent publications 1. Schirmer L, et al. Higher frequencies of HLA DQB1*05:01 and anti-glycosphingolipid antibodies in a cluster of severe Guillain-Barré syndrome. J Neurol. 2016 Aug 2. 2. Paterson RW, et al. Do cerebrospinal fluid transfer methods affect measured amyloid β42, total tau, and phosphorylated tau in clinical practice? Alzheimers Dement (Amst). 2015 Jul 2;1(3):380-4. 3. Granerod J, et al. Neuroimaging in encephalitis: analysis of imaging findings and interobserver agreement. Clin Radiol. 2016 May 13. 4. Lunn MP, Ellis L, Hadden RD, Rajabally YA, Winer JB, Reilly MM. A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies. J Peripher Nerv Syst. 2016 Mar;21(1):33-7. 5. Lunn MP, Van den Bergh PY. Outcome measures in neuromuscular disease: is the world still flat? J Peripher Nerv Syst. 2015 Sep;20(3):255-9. 6. Castillo JJ, et al Central nervous system involvement by Waldenström macroglobulinaemia (Bing-Neel syndrome): a multi-institutional retrospective study. Br J Haematol. 2015 Dec 21. 7. Paterson RW, et al. Dissecting IWG-2 typical and atypical Alzheimer's disease: insights from cerebrospinal fluid analysis. J Neurol. 2015 Dec;262(12):2722-30. 8. Vanhoutte EK, et al. Rasch-ionale for neurologists. J Peripher Nerv Syst. 2015 Sep;20(3):260-8. 9. Van den Bergh PY, Lunn MP. Future needs in peripheral neuropathy outcome measures. J Peripher Nerv Syst. 2015 Sep;20(3):341-6.

Key grants awarded 1. Welcome Equipment Grant – SIMOA £200000 2015 2. Investigation of outcome biomarkers in Guillain-Barre syndrome £30000 2 years 2015 3. Cochrane Neuromuscular Disease Group Quinquennial Renewal £700000 5 years 2014 4. Motor Neurone Disease Association- Small Grants £9000 (total) 3 years 2012 5. GBS Support Group Small Grants - £9000 (total) 3 years 2012 6. Wolfson Centre for Neurodegeneration – co-applicant 20m 5 years 2011 7. Biomarker Discovery Grant – Anon – (PIs Hardy, Fox, Lunn) 325000 2 years 2011

5 | P a g e James Miller

Current Role Consultant Neurologist, Specialist interest – Neuromuscular Disorders Department of Neurology, Royal Victoria Infirmary, Newcastle Upon Tyne Hospitals

Research profile Current Research Studies: 1. Local PI for NIHR CSP 23564. UKMyonet. Identification of disease susceptibility genes associated with development and clinical characteristics of primary inflammatory muscle diseases, PM, DM and IBM. 2. Local PI for NIHR CSP 87344. IGOS. Clinical and biological determinants of disease course in Guillain-Barre syndrome: a prospective UK-wide observational study interfacing with the International Guillain-Barre syndrome Outcome Study – IGOS. 3. Local PI for NIHR CSP: 131148. RESILIENT. A randomized, double-blind, placebo- controlled, multicenter, parallel group, dose-finding, pivotal, phase IIb/III study to evaluate the efficacy, safety and tolerability of intravenous BYM338 in patients with sporadic inclusion body myositis. 4. Local PI for NIHR ID 13228.Using Next Generation Sequencing to Unravel the Pathogenesis of Sporadic Inclusion Body Myositis (IBM) International - IBM Consortium Genetic Study. This very large collection of DNA will allow more detailed genetic studies to understand the genetic risks factors for this disease. Previous research: 1. UK CI for NIHR 13446. FORCIDP. A double-blind, randomized, multicenter, placebo controlled, parallel-group study to evaluate the efficacy and safety of fingolimod in patients with CIDP. 2. Arthritis Research Campaign Clinical Research Fellow, MRC Centre for Infection and Immunity, Dept of Rheumatology, University of Birmingham (1996-1999). “A comparison of the inflammatory infiltrate after eccentric exercise damage and polymyositis.” This research formed the basis of my PhD thesis.

Selected recent publications 1. Rose MR, Jones K, Leong K, Walter MC, Miller J, Dalakas MC, Brassington R, Griggs R. Treatment for inclusion body myositis. Cochrane Database of Systematic Reviews 2015, Issue 6. Art. No.: CD001555. DOI: 10.1002/14651858.CD001555. 2. J.A.L. Miller, A. Spyropoulos, E. Jaros, F. Galban-Horcajo, R. G. Whittaker and H. J. Willison. Anti-GQ1b ganglioside positive Miller Fisher syndrome – evidence of paranodal pathology on nerve biopsy. Journal of Neuromuscular Diseases V2 2015. 3. Rodríguez Cruz PM, Luo YB, Miller J, Junckerstorff RC, Mastaglia FL, Fabian V. An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies. Neuromuscul Disord. 2014 Jun 30. PMID: 25153265. 4. Whittaker, R.G., Chinnery, P.F. and Miller, J.A.L. “Teaching Neuroimages: Muscle cramps and a raised creatine kinase.” Neurology 2014 Jun 17;82(24):e220-1. 5. Rygiel, K., Miller, J., Grady, J., Rocha, M., Taylor, R., Turnbull, D.M. "Mitochondrial and inflammatory changes in sporadic Inclusion Body Myositis" Neuropathology and Applied Neurobiology 2014 Apr 18 PMID: 24750247. 6. Rose MR; ENMC IBM Working Group. 188th ENMC International Workshop: Inclusion Body Myositis. Neuromuscul Disord. (2013) Dec;23(12):1044-55. 7. Pfeffer G, Elliott HR, Griffin H, Barresi R, Miller J, et al. Titin mutation segregates with hereditary myopathy with early respiratory failure. Brain. 2012 Jun;135 (Pt6):1695-713.

6 | P a g e Appendix 3. Grants won by Centre PIs since renewal (2013)

> 250 awards

Total award value >70m

Andrew Blamire

EU – Horizon 2020 VISION-DMD - Phase 2 Clinical Trials of VBP15: An Innovative Steroid-like Intervention on Duchenne Muscular Dystrophy Prof K Bushby, Dr ME Guglieri, Dr KG Hollingsworth, Prof AM Blamire, Prof VW Straub, other European partners Oct 2015-Sep 2019 £1,832,756

ARUK Dissecting the tripartite relationship of fatigue, autonomic dysfunction and immune dysregulation Prof Fai Ng, Prof AM Blamire, Dr Mark Baker, Dr Stuart Watson, Professor Steven Rushton, Dr Peter Gallagher, Dr John-Paul Taylor Apr 2016-Sept 2018 Amount: £160,000

MRC Confidence in Concept In vivo human motor unit imaging Prof AM Blamire, Dr R Whittaker, Dr I Schofield July 2016-Apr 2016 Amount £17,748

MRC Confidence in Concept Development of translational biomarkers of glutamate dysfunction in brain tumour related epilepsy Dr M Cunningham (PI), Prof AM Blamire, Dr MR Baker, Dr GS Gorman Sept 2016-Sept 2017 Amount: £53,143

EU FP7 BIOIMAGE-NMD Novel imaging technologies for muscle disease €5.96million

Kate Bushby

European Commission RD-ACTION Joint Action on EU wide rare diseases information databases Jun 2015 – May 2018 £530,404.00

Muscular Dystrophy UK (Formerly Muscular Dystrophy Campaign) TREAT-NMD Advisory Committee for Therapeutics Oct 2015 – Sep 2016 £10,000.00

Alex’s Wish Clerical Assistant post as part of the 'Newcastle plan' initiative Apr 2016 – Mar 2017 £28,913.43

1 | P a g e Muscular Dystrophy Group of GB MDC Clinical Trials Coordinator, Newcastle Feb 2016 – Feb 2021 £38,947.00

PTC Therapeutics International Limited Costing for PTC Feb 2016 – Feb 2018 £404,809.65

Commission of the European Communities RARE – Best practices October 2013 – December 2016 £28,571

European Commission TREAT-NMD Operating Grant January – December 2013 Split award value £35,657

NIHR Senior Investigator Award April 2013 – January 2018 £75,000

Great Ormond Street Hospital Children’s Charity Improving standards of care and translational research in spinal muscular atrophy April 2013 – March 2015 £29,507

Muscular Dystrophy Campaign MDC Clinical Trials Coordinator June 2013 – June 2015 £75,335

Muscular Dystrophy Campaign High throughput sequence analysis to identify genetic causes of limb girdle muscular dystrophies October 2013 – September 2016 £60,000

Duchenne Parent Project DMD liaison post at TREAT-NMD office October 2013 – March 2014 £18,518

Parent Project Muscular Dystrophy DMD Liaison post at TREAT-NMD office April – September 2014 £22,500

Children’s National Medical Center Project 3 – accelerating the agenda for academic networking in post marketing surveillance for RD

2 | P a g e Drug development January – December 2014 £88,888

Patrick Chinnery

Wellcome Trust Senior Fellowship Enhancement What determines the switch from glycolytic to oxidative metabolism in the developing germ line? PI101876/B/13/A £198K

National Institute for Health Research – Rare Diseases Translational Research Collaboration. Disease progression in mitochondrial disease. £200K

National Institute for Health Research – Senior Investigator Award Renewal PI NF-SI-0514-10016 £45K

MRC Confidence in Concept. Bezafibrate to treat mitochondrial myopathy. Internal award. PI 100% £69K

GlaxoSmithKIine. Novel biomarkers for mitochondrial disease PI 100% £197,219

Medical Research Council Clinical research capabilities call. The Newcastle University Single Cell Unit (NUSCU) £1.98M.

Wellcome Trust Clinical Research Training Fellowship to Dr Michael Keogh (103396/Z/13/Z) The role of inherited and acquired mitochondrial DNA mutations in dementia with Lewy bodies £221K

Wellcome Trust Senior Clinical Fellowship 2nd Renewal (101876/Z/13/Z) Genetic factors modulating the expression of mitochondrial disease £1.3M

Medical Research Council Maximising the value of MRC Brain Banks: high-throughput genomic studies to enrich data available to the research community. £1.7M

Medical Research Council High throughput genomics and transcriptions of the human development biology resource. £891K

3 | P a g e Wellcome Trust Clinical Research Training Fellowship to Dr Peter Kullar Defining the cellular and molecular mechanisms of mitochondrial deafness £225K

Chris Clark

The Commission of the European Communities FP7-HEALTH-2013-INNOVATION-1 BIOIMAGE-NMD December 2013 – December 2016 £498,992

UCL Capital Equipment State of the art magnetic resonance imaging October 2013 £250,000

Giulio Cossu

Wellcome Trust Institutional Strategic Support Fund [WT ISSF] Nanoparticle-mediated silencing of endothelial adhesion junctions to favour systemic delivery of stem cells. A pilot study 01/03/2016 – 30/09/2016 £28,000

Wellcome Trust (Health Innovation Challenge fund) Pre-clinical development of a stem cell based gene therapy protocol and clinical proof of principle for Duchenne Muscular Dystrophy 01/06/2016 – 31/05-2018 £814,550.00

*Maratò (Spanish Foundation) New Stem Cell therapies for Duchenne Muscular Dystrophy £100,971

British Heart Foundation (PG/14/1/30549) Fate and potency of pericytes in the development and the repair of the heart £261,056

European Community EC FP7 IP 262948 Development of standard scaffolds for the rational design of bioactive materials for tissue regeneration (Biodesign) €561,000

Michael Duchen

Wellcome Trust (2015) equipment grant: The Dynamic Cell: A High-Speed High-Resolution Microscopy Platform for Biomedical Imaging £490,000 (£290,000 from WT, £200,000 MRC match funded)

4 | P a g e Kephalos Research Fund (2014-15) supporting ‘mitochondrial research’ $300,000

BBSRC 2014-2017. In situ quantification of metabolic function using fluorescence lifetime imaging. PI in Collaboration with Gyorgy Szabadkai, Angus Bain (Physics) £639,625

Parkinson’s UK (K-1107) Abnormal lysosomal calcium signalling in Parkinson’s disease: clues from lysosomal storage disorders Co-applicant with Sandip Patel and Tony Schapira June 2012-March 2014 £21,643

SLMS capital equipment fund. ‘to develop a high throughput high content imaging platform at UCL’ 2013 £300,000

GSK/BBSRC CASE PhD studentship Mitochondria as therapeutic targets in human disease 2013-2107 £101,520

Action Medical research Mitochondrial quality control pathways as therapeutic targets in genetic mitochondrial disease 2013-2016 £200,243

Eisai Therapeutic Innovations Group (TIG) Funding for screening mPTP inhibitors 2 positions for 3 years plus consumables 2014-2017

GSK: 2014-2015 post-doctoral appointment: To develop small molecule inhibitors of the permeability transition pore £143,000 (to be funded on an annual basis but with promise of renewals)

EPSRC Post-doctoral fellowship for Tom Blacker for 1 year 2013-2014

Two UCL Grand Challenge studentships Jointly with Kenneth Smith 2013-2016

Elizabeth Fisher

MRC Novel and bespoke mouse models for dissecting neurodegenerative disease With Linda Greensmith, Giampietro Schiavo, Abraham Acevedo-Arozena, Pietro Fratta, Adrian Isaacs, Frances Wiseman April 16 to Mar 20 award number MC_EX_MR/N501931/1. £1,781,285.36

5 | P a g e Rosetrees Foundation 24 months from March 2015 to February 2017 A novel approach to determining the role of axonal RNAs in motor neuron disease (amyotrophic lateral sclerosis) £9601

American Association (Fisher 15 IIP-198) August 2014 – July 2015 A new humanised delta-14 mutant mouse model for dissecting the pathobiology of FUS-ALS. $80,000

Motor Neurone Disease Association Fisher (10/442) PhD studentship Characterising a novel delta14 Fus mouse model 3 years from Oct 2014 to Sept 2017 With Dr Abraham Acevedo £112,690

Medical Research Council MR/L021056/1 36 months from Sept 2014 to August 2017 New humanised mouse models for dissecting the pathobiology of disease, using FUS-ALS as a paradigm £994,155

Alzheimer’s Society PhD studentship PhD studentship 3 years from Oct 2014 to Sept 2017 Finding new molecular pathways in Alzheimer Disease £84,990

UCL PhD studentship (Simone Granno) PhD studentship 3 years from Oct 2013 to Sept 2016 The role of Wnt signalling in amyloid peptide processing in a down syndrome mouse model presenting abeta pathology with implications for the treatment of dementia (￡32,535 from the School and ￡32,535 from the UCL Impact studentship scheme) and ￡1000 consumables per year

Epilepsy Research UK 20 months August 2013 to March 2014 A mouse model of seizures in Down syndrome/Alzheimer disease £29,897

Medical Research Council MR/K018523/1 30 months from April 2014 to Sept 2016 Investigating a neuronal subcellular transcriptome by the novel technique of RNA TU-tagging, in a normal and ALS-related mouse model £466,205

Alzheimer’s Research UK PhD studentship 3 years from Oct 2013 to Sept 2016 (Laura Pulford) Understanding Alzheimer's disease using mouse models of Down syndrome £105,250

Wellcome Trust Joint Senior Investigators Award 7 years from January 2014 to December 2020

6 | P a g e Understanding Down syndrome phenotypes through innovative mouse genetics £1,258,241

Wellcome Trust Strategic Award 5 years from Jan 2013 to December 2017 The London Down Syndrome Consortium (LonDownS): An integrated system to study the development and therapeutic amelioration of cognition and dementia. £838,709.40

Xavier Golay

Olea Medical Processing pipeline for CEST Imaging Funding Period: October 2015 – September 2019 £94,888

SBRI NHS England A Gold Standard Perfusion Phantom for Quantitative MRI Jan 2016 – Dec 2016 £1,000,000

Wellcome Trust UNS16884 Multi-User Ultra-High Field Clinical Imaging Research Centre for London Jan 2017 – Dec 2021 £4,000,000

MS Society Grant #44 (PI: J. Greenwood; CoIs: R. Nicholas, X. Golay, M. Michaelides, J. Chataway, V. Calder, O.Ciccarelli) High dose Simvastatin treatment for Secondary Progressive Multiple Sclerosis: Impact on vascular perfusion and oxidative damage Jan 2016 – Dec 2017 £314,179

SBRI NHS England A Gold Standard Perfusion Phantom for Quantitative MRI £100,000

UCL Therapeutic Innovation Fund GlucoCEST as an ictal MRI method in epilepsy £59,802

Chiesi Pharmaceutical (PI: N. Robertson, CoI: X. Golay) Development of Melatonin as an Adjunct Therapy for Neonatal Encephalopathy Chiesi £1,600,000

National MS Society - US # RG 5056A4/1 (PI: K. Smith, CoI: X. Golay) Towards a greater understanding of multiple sclerosis: recognising the importance of hypoxia, and new opportunities for therapy NMSS $606,000

Wellcome Trust HICF WT103709 (PI: P. Nachev, CoIs: S.Ourselin, G. Rees, R, Jaeger, X. Golay Synopion: a system for automatic anomaly quantification for brain imaging triage and classification WT/DoH £1,500,000

MRC MR/M006743/1 (PI: N. Robertson, CoIs: X. Golay, D. Peebles, H.E.G. Hagberg, I. Tachtsidis, C. Tann, A. Galkin, N. Klein, P. Gressens, B.W.W. Kramer, T. Wolfs, B. Fleiss) MRC £1,256,000

7 | P a g e MRC MR/M009106/1 (PI: T. Yousry, CoIs: N. Fox, S. Ourselin, D. Alexander, N. Weiskopf, J. Thornton, J. Warren, X. Golay) MRC £ 1,217,000

MRC MR/M009092/1 (PI: M. Emberton, CoIs: D. Gadian, S. Punwani, M. Lythgoe, D. Hawkes, T. Ng, X. Golay, I. Gout, M. Rodriguez-Justo, C. Swanton) MRC £5,300,000

Grainne Gorman

NIHR-BRC funding: Exercise training in sedentary subjects: Assessing the benefits and impact on sarcopenia 2013 – 2016 PI: Gorman; total award £107,988

MRC Centre for Neuromuscular Disease in Children and Adults at UCL and Newcastle Newcastle component Turnbull DM, Bushby K, Gorman G, Horvath R, Lochmüller H, McFarland R, Straub V, Taylor RW, 2014 – 2018 Total award: £1,333,746

2016-2017 NIHR Biomedical Research Centre Mitochondrial Disease and Sports Physiology Collaboration Co-PI with Turnbull £101,109

MRC Confidence in Concept “Mechanistic evaluation of stroke and mitochondrial dysfunction” 2015-2016 Co-PI with McFarland £67,000

Collaborative FP7 Project Observational Prolonged Trial in Myotonic dystrophy type 1 to Improve QoL-Standards, a Target Identification Collaboration. (Newcastle PI: Gorman) 3-year project £233,400

Linda Greensmith

Orphazyme Research Grant Investigating novel therapeutic agents in models of IBM and multisystem proteinopathy in vitro and in vivo 2015-2017 £229,093

Foundation Thierry Latran Deficits in axonal transport as a target for pharmacological intervention in Amyotrophic Lateral Sclerosis 2015-2017 €117,000

Food and Drugs Administration Agency (USA) Phase II Trial of Arimoclomol in IBM 2015-2019 $1,582,887

8 | P a g e MRC Research Grant Molecular chaperone function and motor neuron degeneration 2015-2018 £688,449

Motor Neuron Disease Association The role of miRNAs in ALS and their use as a biomarker of disease progression 2016-2019 £229,328

MRC Programme Grant Novel and Bespoke Mouse Models for Dissecting Neurodegenerative 2016-2021 £1.78M

AFM-Telethon Targeting molecular pathways of disease in SBMA 2016-2018 €100,000

The Graham Watts Bequest Program Grant for Research into Motor Neuron Disease 2013-2018 £654,000

The Sobell Foundation/Brain Research Trust £175,000 2013-2018

Motor Neuron Disease Association A targeted proteomic analysis for biomarkers discovery in ALS A Malaspina, I Pike and L Greensmith £135,408 2013-2016

UCL Hospitals Biomedical Research Centre Neuroscience Programme The role of sphingolipids in the pathomechanism of hereditary sensory neuropathy type 1 HSN1 M Reilly (PI), M Laurá, B Kalmar and L Greensmith £96,360 2013-2015

Medical Research Council New humanised mouse models for dissecting the pathobiology of disease, using FUS-ALS as a paradigm E Fisher (PI), L Greensmith and G Schiavo £994,155 2014-2017

Motor Neuron Disease Association Optogenetically-controlled restoration of muscle function in MND model mice using engrafted ES- derived motor neurons L Greensmith, B Bryson and I Lieberam £229,160

9 | P a g e 2014-2017

Foundation Thierry Latran Optogenetically-Controlled Restoration of Muscle Function in ALS €160,000 2014-2016

Michael Hanna

Muscular Dystrophy UK Salary for CRA (x2) Jun 2016 – Feb 2017 £60,000

Medical Research Council MRC Centre for Neuromuscular Diseases Centre Renewal 2013-2018 £2.8 million

HEFCE Higher Education Arimoclomol for sIBM proof of concept Innovation Fund 01/05/16 – 31/07/16 US$100,000

UCLH/NIHR BRC Matched funding for MRC Centre for Neuromuscular Diseases 2013-2019 £493,106

GOS BRC Matched funding for MRC Centre for Neuromuscular Diseases With F. Muntoni 2013-2018 £282,714

Lily Foundation Clinical Research fellow 2014-2016 £124,000

Neuromics FP7 Channelopathies – for Karen Stevens 2013-2017 £193,000

UCLH BRC A randomized, double-blind, placebo controlled Fast Track phase IIa experimental pilot trial assessing efficacy of a single dose or repurposed bumetanide in genetically defined hypokalaemic periodic paralysis assessed using the electrophysiological McManus protocol Co grant holder w/ Doreen Fialho 2013-2014 £40,000

10 | P a g e Action Medical Research Mitochondrial quality control pathways as therapeutic targets in genetic mitochondrial disease Co-grant holder w/ Michael Duchen 2013-2016 £192,243

NIHR Rare Diseases Translational Research Collaboration - IBM 2013-2014 £250,000

NIHR Rare Diseases Translational Research Co-grant holder w/ Francesco Muntoni 01/11/13-31/12/14 Mike Hanna Collaboration – DMD £200,000

NIHR Rare Disease TRC Postdoctoral Fellowship IBM – Pedro Machado 2014-2017 £401,333

NIHR Rare Disease TRC Postdoctoral Fellowship Channels – Emma Matthews 2014-2017 £363,060

MRC Periodic paralysis: from molecules to mice Co-grant holder with R Männikkö 2014-2017 £464,146

Wellcome Trust : genetics, biophysics and circuit mechanisms of paroxysmal neurological disorders Co-I 2014-2019 £4,194,451

John Hardy

MRC Understanding the genes for Parkinson's disease

2012-2018 £1,417,253.14

CBD Solutions AB DNA sequence analysis of CBD Karin and Stern Morstedt 2014-2016 £321,165.00

Wellcome Trust The London Down Syndrome Consortium (LonDownS)

11 | P a g e An integrated system to study the development and therapeutic amelioration of cognition and dementia 2016-2021 £83,750.00

Wolfson Biomarker Lab - Linked to 6HBE 2012-2018 £1,663,664.00

Wolfson Foundation Isotope labelling - linked 6HBE 2012-2018 £169,694.00

NIHR NIHR Dementia BRU award 2012-2017 £660,259.00

MSA Development and characterisation of a human pluripotent stem cell (iPSC) derived oligodendrocyte model of MSA 2017 £55,535.00

JPND PERADES: Defining genetic, polygenic and environmental risk factors for Alzheimer's disease using multiple powerful cohorts, focussed and stem perades. 2014-2016 £183,350.00

WTISSF Investing in Excellent Researchers - Daniah Trabzuni matched funding 2014-2015 £13,931.50

JPND Risk and modifying factors in fronto temporal dementia 2014-2017 £250,000.00

Biogen Using genetic variability in whole transcriptome expression in cells and tissues to understand the pathogenesis of neurodegenerative disorders 2014-2017 £250,500.00

NIH NINDS Exome sequencing of pathological disease samples 2014-2017 £233,333.33

Alzheimer Research UK

12 | P a g e Using genetic variability in whole transcriptome expression in the hippocampus and temporal cortex to understand the pathogenesis of Alzheimer Disease 2014-2017 £92,186.00

Alzheimer Research UK Fellowship Pablo Garcia Reitboeck 2015-2018 £223,782.94

Innovate UK through Cytox The utility of the MTOR signalling pathway dysregulation and mutational profiling in the risk stratification for future cognitive decline in mild cognitive impairment 2015-2018 £199,555.00

Alzheimer’s Research UK, Alborada Trust Alzheimer's Research UK Stem Cell Research Centre 2014-2016 £150,000.00

MSA Trust Development and characterisation of a human pluripotent stem cell (iPSC) derived oligodendrocyte model of MSA 2015-2017 £55,535.00

Kieren Hollingsworth

Medical Research Council Quantitative Imaging in Juvenile Idiopathic Arthritis March 2017-February 2018 £53,000 (Principal Investigator)

Medical Research Council Understanding the biology of ageing muscle in the oldest old January 2016-August 2016 £21,000 (Co-applicant, 5%)

Medical Research Council Non-invasive quantitative ventilation imaging using fluorocarbon gases August 2016-August 2019 £633,000 (Co-applicant, 5%)

Diabetes UK Overcoming barriers to best management of type 2 diabetes October 2013-September 2018 £1.3m (Co-applicant, 20%)

H2020 VISION-DMD January 2016-January 2019 £1.8m (Co-applicant, 5%)

Newcastle Healthcare Charity

13 | P a g e Pancreas morphology in type 2 diabetes following reversal of diabetes January 2015-December 2015 £36.5k (Co-applicant, 50%)

Rita Horvath

Wellcome Trust Exploring novel molecular targets and disease mechanisms in mitochondrial protein synthesis deficiencies to develop novel treatments in mitochondrial disease Apr 2016 – Mar 2021 £1,152,904.00

Medical Research Council (MRC) Exosomal Protein Deficiencies: How Abnormal RNA Metabolism Results in Childhood-Onset Neurological Diseases Jul 2016 – Jun 2019 £558,443.25

ApoPharma Inc TIRCON2012-EXT UK Nov 2015 – Mar 2018 £23,592.00

Wellcome Trust Investigator Award (109915/Z/15/Z) Project: Exploring novel molecular targets in mitochondrial protein synthesis to develop treatments in mitochondrial disease Mar 2016 – Feb 2021 £1,150,000

Neurosciences and Mental Health Board Grant (MR/N025431/1) Project: Exosomal protein deficiencies: how abnormal RNA metabolism results in childhood-onset neurological diseases Jul 2016 – Jun 2019 £686,866

Co-investigator Newton Fund (UK/Turkey) MR/N027302/1 (co-investigator with Professor Hanns Lochmüller) Project: New genomics approaches to explore the neurogenetic disease burden of consanguineous marriages in Turkey Jul 2016 – Dec 2018 £200.000

Wellcome Trust Pathfinder Award 201064/Z/16/Z (co-investigator with Professor Hanns Lochmüller) Project: Strengthening the neuromuscular junction as a new concept for the treatment of congenital myasthenic syndromes and motor neuropathies with synaptic dysfunction. Apr 2016 – Nov 2017 £170.000

MRC Confidence in Concept Fund (co-investigator with Professor Hanns Lochmüller) Project: Strengthening the neuromuscular junction as a new concept for the treatment of congenital myasthenic syndromes and motor neuropathies with synaptic dysfunction.

14 | P a g e Apr 2016 – Nov 2016 £37,852

European Research Council (ERC) Reversibility and tissue specificity of mitochondrial translation defects in early childhood Starter Grant - Consolidator (309548) Role: PI 2013-2018 £1.139.280.00

FP7-PEOPLE-ITN (Marie-Curie Action) Mitochondrial European Educational Training MEET (317433) Role Co-Investigator with Patrick Chinnery in Newcastle, supervisor of a PhD student 2013-2016 Total £3.042.664, 00, Newcastle: €577,798.57

MRC Confidence in Concept Fund (Newcastle University) Project: Developing experimental therapies for severe childhood mitochondrial diseases Role: PI 01.09.2014-28.02.2015 1 hour/week £19,457.75

Henry Houlden

Ataxia UK: PhD studentship: DNA repair pathways: a common genetic mechanism and potential therapeutic pathway in Spinocerebellar ataxia, Friedreich’s ataxia and Huntington’s disease 01/10/2016 – 31/09/2019 £52,500

Wellcome Trust: development of a next generation sequencing facility at UCL, 01/01/2011 – 31/12/2016 £636,000

UK MSA Trust: UK MSA network to identify MSA clinical cases and create a biobank 01/09/2015 – 31/08/2018 £50,000

USA MSA Coalition: Identification of DNA and RNA biomarkers. 01/05/2016 – 31/04/2019 $100,000

NIHR: using next generation sequencing to identify biomarkers for neurological disorders 01/01/2015 – 31/03/2017 £96,000

Wellcome Trust Synaptopathies: genetics, biophysics and circuit mechanisms of paroxysmal neurological disorders (DMK, K Volynski, S Schorge, MG Hanna, H Houlden, JE Rothman, J Jepson, S Sisodiya, PJ Goadsby) Co-Investigator 2014-2019 £4,194,451

Hanns Lochmüller

15 | P a g e Ultragenyx Pharmaceutical Inc. Identifying HIBM patients – Ultragenyx Sep 2015 – Feb 2017 £156,712.85

Guarantors of Brain Adrenergic signalling and congenital myasthenic syndromes – ABN Fellowship Aug 2015 – Jul 2018 £164,119.00

Biogen Idec SMA prevalence data (Lochmüller) Jul 2015 – Aug 2016 £121,333.33

F Hoffmann-La Roche Limited TREAT-NMD registry (Lochmüller) Aug 2015 – Oct 2015 £8,571.43

Myotubular Trust Myotubular and Centronuclear Myopathy Patient Registry Dec 2015 – Jan 2018 £61,744.00

Ultragenyx Pharmaceutical Inc. Identifying HIBM patients – Ultragenyx Sep 2015 – Feb 2017

Muscular Dystrophy UK (Formerly Muscular Dystrophy Campaign) Purchase of Embletta MPR PSG with ST+ proxy sleep recording device Nov 2015 – Nov 2016 £11,500.00

Medical Research Council (MRC) CiC - Strengthening the neuromuscular junction as a new concept for the treatment of congenital myasthenic syndromes and motor neuropathies with synaptic dysfunction Mar 2016 – Nov 2016 £37,852.00

Myotubular Trust Myotubular and Centronuclear Myopathy Patient Registry Dec 2015 – Jan 2018

Medical Research Council (MRC) CiC - Strengthening the neuromuscular junction as a new concept for the treatment of congenital myasthenic syndromes and motor neuropathies with synaptic dysfunction Mar 2016 – Nov 2016

Ultragenyx Pharmaceutical Inc. International HIBM patient registry 2 (Lochmüller) May 2016 – Apr 2018 £368,000.00

Myotonic Dystrophy Support Group

16 | P a g e Myotonic Dystrophy Registry Jan 2016 – Dec 2016 £5,000.00

Wellcome Trust Strengthening the neuromuscular junction as a new concept for the treatment of congenital myasthenic syndromes and motor neuropathies with synaptic dysfunction Oct 2016 – Mar 2018 £172,797.00

Kindness for Kids Foundation The use of novel linker molecules as a targeted molecular treatment for Congenital Muscular Dystrophy Jun-16 – May 2019 £43,870.97

Medical Research Council (MRC) New genomics approaches to explore the neurogenetic disease burden of consanguineous marriages in Turkey Aug 2016 – Mar 2017 £253,515.00

European Commission TREAT-NMD Operating Grant 2013 – 2018 Split award value £35,657

Medical Research Council (MRC) MRC - Centre for Neuromuscular Diseases 2013 – 2018 Split award value £95,796

Association Francaise Contre les Myopathies Coordination of the global patient registries for neuromuscular disorders 2013 – 2015 £35,714

Duchenne Parent Project Coordination of the global patient registries for neuromuscular disorders 2013 – 2015 £15,892

European Commission 3GB-test proposal 2013 - 2014 £9,019

Eli Lilly and Co (USA) Lilly & Co (USA) 2013 – 2014 £70,000

Jennifer Trust for Spinal Muscular Atrophy Jennifer Trust UK SMA Co-ordinator 2013 - 2014

17 | P a g e £10,000

PTC Therapeutics, Inc. Patient Registry (Lochmüller) 2013 – 2013 £10,826

Action Duchenne Building the Knowledge Base for Therapy Development in Duchenne Muscular Dystrophy 2015-2020 £250,000

Association Francaise Contre les Myopathies Validation of Serum Biomarkers for DMD 2015-2016 £21,230

British Heart Foundation Deep molecular phenotyping of myotonic dystrophy (DM1) hiPSC-cardiomyocytes to facilitate risk stratification and drug evaluation 2015-2018 £72,413

Marigold Foundation Ltd Naarden Five Years Later. A global assessment of myotonic dystrophy registries, databases and cohorts. 2015-2016 £20,000

Medical Research Council (MRC) CiC: Developing an assay to measure SMN complex activity for the identification of SMA therapeutics. 2015-2016 £19,565

National Cancer Institute National Institute of Cancer collaboration - UK Myotonic Dystrophy Patient Registry 2014-2015 £13,889

National Institute for Health Research (NIHR) PhenoDM1Myotonic Dystrophy type 1 (DM1) deep phenotyping to improve delivery of personalised medicine 2015-2017 £192,000

Newcastle upon Tyne Hospitals NHS Foundation Trust (NUTH)(Main) Dr Michela Guglieri RCF Support 2017-2019 £153,755

Ultragenyx Pharmaceutical Inc. Identifying patients – Ultragenyx 2015-2016 £137,600

18 | P a g e Wellcome Trust Controlling Abnormal Network Dynamics with Optogenetics (CANDO) - Full Application £7,337,845

Dimitri Kullmann

Medical Research Council Gene therapy for refractory epilepsy (DMK, S Schorge, MC Walker) 2014-2019 £3.1m

Wellcome Trust Synaptopathies: genetics, biophysics and circuit mechanisms of paroxysmal neurological disorders (DMK, K Volynski, S Schorge, MG Hanna, H Houlden, JE Rothman, J Jepson, S Sisodiya, PJ Goadsby) 2014-2019 £4,194,451

Medical Research Council Periodic paralysis: from molecules to mice (R Mannikko, DMK, MG Hanna, S Schorge) 2014-2017 £467,547

Marie-Curie Fellowship for A. Lieb. 2016-2018

Wellcome Trust Sir Henry Wellcome Fellowship for D Kaetzel “Optogenetic dissection and treatment of diseased neural circuitry.” 2013-2016 £250,000

F Hoffmann-La Roche Ltd. Roche Postdoctoral Fellowship for Amy Wolff “Optogenetic and chemogenetic dissection and treatment of neural circuitry in schizophrenia.” 2013-2015 £203,320

Wellcome Trust Clinical Research Training Fellowship for U Vivekananda “Presynaptic neurological channelopathies” 2013-2015 £192,126

Wellcome Trust Clinical Postdoctoral Fellowship for S Crisp “Pathological mechanisms in human disorders of glycinergic transmission” 2013-2016 £335,334

19 | P a g e Brain Research Trust PhD studentship for Jonathan Cornford 2013-2016

Epilepsy Research UK Optogenetic control of GABAergic interneurons during epileptiform activity 2013-2015 £137,800

MRC Activity-dependent regulation of synaptic strength and cellular mechanisms of (KE Volynski, I Pavlov, DMK) 2015-2018 727,994.45

European Commission Marie-Curie Fellowship to Gabriele Lignani 2015-2017

Mike Lunn

Cochrane Neuromuscular Disease Group Quinquennial Renewal 2014 – 2019 £700,000

SIMOA analyser in Neuroimmunology/Leonard Wolfson Neurodegenerative biomarkers project – Wellcome Equipment Grant - £200000

Robert McFarland

MRC Confidence in Concept Mechanistic evaluation of stroke and mitochondrial dysfunction 2015 – 2016 £67K

Wellcome Trust Public Engagement Programme 2014 – 2017 £287K Co-PI

Ryan Stanford Appeal PhD Studentship ‘Fight Alpers’ 2014-2017 £50K Co-PI

Lily Foundation Award, Improving the molecular genetic diagnosis of mitochondrial disease 2014-2017 £211K Co-PI

NIHR RCF Award Development and evaluation of a national diagnostic strategy for paediatric mitochondrial disease 2013-2014

20 | P a g e £49K. Co-PI

Jenny Morgan

Muscular Dystrophy Campaign. The effect of modulating the dystrophic skeletal muscle environment on donor stem cell engraftment. P.I (Co-applicant Dr Silvia Torelli 2014-2018 £111,225

UCL Therapeutic Innovation Fund Pharmacological inhibition of programmed necrosis in dystrophic skeletal muscle 2014-2015 £47,077

Muscular Dystrophy Campaign Mechanisms of myonecrosis in Duchenne Muscular Dystrophy: can we control the death of muscle fibres? 2014-2017 £174,944

Francesco Muntoni

MRC Neuromuscular Translational research centre Grant MRC Muntoni Co-PI £3,000,000 2013-2017

Horizon 2020 Neuromics € 300000 (at UCL) Muntoni UK PI 2013-2017

SMA Trust Improving standards of care and translational research in SMA £ 264,000 Muntoni PI 2013-2016

NIHR Rare Disease Initiative Neuromuscular Diseases: Deep Duchenne muscular dystrophy phenotyping Muntoni PI 2013-2016 £355,000

Cure CMD Serum miRNA in dystroglycanopathies Muntoni PI 2014-2106 $ 25,000

MRC

21 | P a g e Peptide Conjugated oligonucleotides for splice switching therapy of SMA Wood PI, Muntoni Co-PI 2014-2017 £1,008,000

AFM A multicentre natural history study on DMD Muntoni Coordinator and CI 2014-2017 € 852,000

Genethon Pre-U7 natural history study Muntoni PI £ 50,836 2014-2016

MDC Allele-selective suppression by antisense oligonucleotide as a therapeutic strategy for collagen VI- related congenital muscular dystrophy Muntoni PI 2014-2016 £115,861

Horizon 2020 Bioimage Muntoni UK co-PI 2013-2017: € 100000 (at UCL)

Horizon2020 eNHANCE motor function in physically disabled people Muntoni UK PI, 2015-2018 £345,000

SMA Europe Identification of as biomarkers and potential therapeutic targets in spinal muscular atrophy Muntoni PI 2015-2017 108,000€

GOSH Charity Vascular abnormalities in Spinal Muscular Atrophy Muntoni PI 2015-2017 £ 99,500

Muscular Dystrophy UK Repair of duplications in dystrophin using CRSIPR/ Cas9 Muntoni PI 2015-2017 £118,4000

22 | P a g e Great Ormond Street Hospital Charity Development of new Gene Therapy approaches for Spinal Muscular Atrophy PhD Studentship 2015-2017 £ 76,000

Horizon2020 EPIBSC An European Bank for induced pluripotent Stem Cellsat UCL Muntoni PI 2016-2017 £300,000

Roche RO6885274 in SMA PI 2015-2016 £74,557

ISIS Pharmaceutics Clinical Efficacy and Safety of ISIS396443 2015-2016 £32,611

Pfizer Anti-GDF8 antibody in Duchenne Muscular Dystrophy PI 2015-2017

Summit C1004 A phase II study of C1100 in Duchenne Muscular Dystrophy 2016-2017

Esperare A phase Ib study of Rimeporide in DMD 2017-2018

Summit C1005 A Phase I study of a new formulation of C1002 in DMD Chief Investigator 2016

Roche Olesoxime open label extension in SMA PI 2016-2017

Gita Ramdharry

Kingston University Small research grant: £4k 2016

NIHR Research for Patient Benefit grant based at UCLH NHS trust. Principle Investigator.

23 | P a g e Aerobic training in neuromuscular diseases. (grant number PB-PG 0711-25151-G613) £52K grant extension

Charcot Marie Tooth UK charity Principle Investigator Home based balance training for people with Charcot Marie Tooth Diseases: A feasibility study £31K for one year study

Clinical Research Network Funding for a 6 month research physiotherapist £17,561

NIHR Research for Patient Benefit grant based at UCLH NHS trust. Principle Investigator. Aerobic training in neuromuscular diseases. (grant number PB-PG 0711-25151-G613) £194K

Co-applicant for NIHR HTA grant [13/30/02] Orthotic management of instability of the knee in neuromuscular disease. PI Dr Catriona Mcdaid, University of York £158,860

Clinical Research Network funding for a 6 month research physiotherapist £19,006

Mary Reilly

NIH RDCRC grant for “Inherited Neuropathy Consortium” (CO-PI) 2015-2019 approx. $5 million

MDA USA Understanding early-onset neuropathies using genome and transcriptome sequencing: 2016 -2019 £164,580

MRC Training fellowship for Dr Umaiyal Kugathasan HSN1 secondary to SPTCL1/SPTLC2 mutations: Pathogenesis and treatment 2014-2017 £144,849

CMT UK grant for MRI scanning 2013- 2016 £30,000

BRC Hereditary Sensory Neuropathy type 1 (HSN1): exploring the role of 1-deoxysphingolipids (1-dSLs) in the pathogenesis of the disease and defining outcome measures for a clinical trial. PI 2013-2015 £99,360

24 | P a g e MRC Centre grant renewal for London Newcastle Centre for Neuromuscular disease (Co-Director) 2013-2018 £2.8 million

Giampietro Schiavo

MRC Programme Grant Novel and bespoke mouse models for dissecting neurodegenerative disease. MR/N501931/1. To: EL Fisher, L Greensmith, G Schiavo, A Isaacs, P Fratta, F Wiseman and A Acevedo 2016 - 2020 £1.78M

Horserace Betting Levy Board. Why do horses roar? From the beginning to the end of recurrent laryngeal neuropathy. To: R Piercy, A. Draper, J. Cheetham, G Schiavo, S Brown and J Perkins. 2016 - 2018 £97,867

NC3Rs Fellowship. A new Drosophila-based strategy to study mitochondrial transport and neuronal ageing in vivo. To: Dr A Vagnoni. 2016 - 2019 £195,000

The Wellcome Trust Postdoctoral Training Fellowship for Clinicians “Control of receptor trafficking as a therapeutic target in the inherited neuropathies” 110043/Z/15/Z. To: A Rossor and G Schiavo. 2016-2019 £412,604

MNDA PhD Fellowship. Regulation of intracellular traffic by TBK1 and its relevance to Amyotrophic Lateral Sclerosis. To: G Schiavo and P Fratta. 2016 -2019 £92,842

MRC Clinical Fellowship Investigating deficits of axonal RNA metabolism and axonal signalling in ALS To P. Fratta. 2015-2019 £1,156,170

Fondation Thierry Latran. Deficits in axonal transport as a target for pharmacological intervention in Amyotrophic Lateral Sclerosis. To: G Schiavo and L Greensmith. €117,000 for 18 months

The Wellcome Trust. Senior Investigator Award £1.74M for 5 years

Alzheimer’s Research UK – UCL Drug Discovery Institute. Lead Academic Scientist (with B. De Strooper and J. Hardy).

25 | P a g e £10M for 5 years

Medical Research Council’s UK Dementias Platform (UKDP). Co-PI (UCL Chairman: T.T. Warner). £1.9M for the set-up of a new high-throughput phenotypic cell screening facility

BBSRC Industrial CASE PhD Fellowship. Mechanisms controlling the axonal retrograde transport pathway. To: G Schiavo and L Greensmith. £92,694 for 48 months

Sir Henry Wellcome Fellowship (to Dr J Sleigh). The Welcome Trust. Dissecting Neuronal Specificity in Hereditary Neuropathy. £250,000 for 48 months

Stephanie Schorge

MRC Programme grant Gene therapy for refractory epilepsy PI: D Kullmann, Co-Is: S Schorge, M Walker 2013 £3.1M

Wellcome Trust Strategic Award Synaptopathies: genetics, biophysics and circuit mechanisms of paroxysmal neurological disorders PI: D Kullmann 2014; 5 Years ~£4.2M.

MRC research grant Functional significance of neuronal sodium channel splicing in epilepsy and pain 2013 £500,156

European FP7 grant EpiMiRNA Partner (Work package leader and UCL PI). 2013 Total funding to to UCL £~400,000

Royal Society University Research Fellowship (renewal) Changing ion channels in the development and treatment of disease £400,000

Volker Straub

Duchenne Now Testosterone Therapy in DMD Nov 2015 – Jan 2018 £172,114.00

Muscular Dystrophy UK (Formerly Muscular Dystrophy Campaign) Brain imaging and cognition in boys with Duchenne muscular dystrophy Oct 2015 – Sep 2018 £55,337.00

RCF Support

26 | P a g e Newcastle upon Tyne Hospitals NHS Foundation Trust (NUTH) £153,755

Jesse’s Journey Second generation exon-skipping therapy combined with pharmacological inhibition of the sodium- hydrogen exchanger: effects on cardiac and skeletal muscle in a mouse model of DMD. Feb 2015 £98,623

LGMD2I Research Fund Charities MYO-SEQ £22,856 Dec 2014

Muscular Dystrophy UK (Formerly Muscular Dystrophy Campaign) Brain imaging and cognition in boys with Duchenne muscular dystrophy Nov 2014 £55,337

Association Francaise Contre les Myopathies Advances in oligonucleotide-mediated exon skipping for DMD and related disorders - WP3 Aug 2014 £94,613

Ultragenyx Pharmaceutical Inc Ultragenyx MYO-SEQ Jun 2014 £202,087

Action Duchenne Building the Knowledge Base for Therapy Development in Duchenne Muscular Dystrophy May 2014 £250,000

Action Duchenne Exosomes: a novel therapeutic approach for the treatment of dystrophinopathies Jan 2014 £71,411

COST Office Applications of MR imaging and spectroscopy techniques in neuromuscular disease: collaboration on outcome measures and pattern recognition for diagnostics and therapy development Dec 2013 £128,688

Genzyme Europe B.V. Genzyme MYO-SEQ (Straub) Nov 2013 £224,542

Medical Research Council (MRC) Peptide conjugated oligonucleotides for splice switching therapy of Spinal Muscular Atrophy Jul 2013 £24,547

27 | P a g e Medical Research Council (MRC) MRC - Centre for Neuromuscular Diseases Jun 2013 £957,958

NCLE HOSPITALS NHS Steriod Therapy £49,719

MUSCULAR DYSTROPHY Fibre Damage £223,472

NEWCASTLE HEALTHCARE Targets of SMN1 £44,186

FED MINISTRY OF EDUC German Musc Dyst Network £20,413

ASSOC FRANCAISE Fututin and FKRP Genes £13,393

ACTION DUCHENNE TREAT COMM OF EUROPEAN Antisense Oligonucleotides £31,923

EUROPEAN COMMISSION NMD Chip £68,966

ASSOC FRANCAISE Zebrafish Models £29,204

DUCHENNE IRELAND AONs in Mouse Models £62,160

ASSOC FRANCAISE In-Vivo Sarcolemmal £27,040

EUROPEAN COMMISSION CARE-NMD £176,877

AVI BIOPHARMA INC AVI Biopharma £86,038

28 | P a g e MULTI Oligonucleotide Technology £70,866

PARENT PROJECT MUSCU Research in Duchenne Muscular Dystrophy £9,000

EUROPEAN COMMISSION TREAT NMD Operating Grant £142,629

ASSOC FRANCAISE MDEX Consortium WP3 Extension £94,61

Rob Taylor

The Lily Foundation PhD studentship The evaluation of novel mitochondrial disease genes identified by whole exome sequencing. co-PI with Dr R. McFarland 2016-2019 £71,200

The Lily Foundation Diagnosis of mitochondrial disease using whole exome sequencing. co-PI with Prof D.M. Turnbull and Dr R. McFarland £90,000

MRC Molecular Pathology Node Call The Newcastle Proximity Laboratory PI Prof A.G. Hall, co-investigator; £3.8M total funding award

NIHR Newcastle Biomedical Research Centre Project Funding Improving the diagnosis of mitochondrial respiratory chain dysfunction using quantitative immunohistochemistry PI with Dr K Rygiel £100,176

John Thornton

Medtronic Inc., Demonstrating state-of-the-art neurological MRI for patients with DBS equipment in situ consistent with new product-label MRI safety conditions PI £40,234 2015

UCLH NIHR BRC Neuroimaging Initiative staff support award PI £174,398 2014-17

29 | P a g e UCL Neuroscience ZNZ Collaboration grant: Improving imaging for preoperative neurosurgical targeting and intraoperative image guidance Thornton Co-I, PIs T. Yousry, R Tuura £10,000 2014

MRC Next generation MRI brain imaging platform for dementia research: from microstructure to function Grant to substantially upgrade research MRI platform Co-I, PI T. Yousry £1.4M 2014

UCLH NIHR BRC Neuroscience Programme Big Questions Funding Call; Novel biomarkers in amyotrophic lateral sclerosis Co-I, PI L. Greensmith £251,259 2014-2017

Michael Trenell

National Institute for Health Research; National Health Innovation Observatory PI and Director Jun. 2016 £10,001,000

Medical Research Council / Unilever CASE Studentship exploring sleep and metabolism Oct. 2015 £122,000

European Institute for Innovation and Training; Delivering digital diabetes care at scale across Europe (with Philips, Achmea, & German National Diabetes Centre). Sept. 2015 £742,000

Sport England / National Lottery; Move into Sport. Apr. 2013 £155,000

ESRC / Alzheimer’s Society Standing up for Dementia: exchanging knowledge on developing a patient and professional pathway for physical activity and exercise. Jan. 2013

£120,000 NIHR Biomedical Research Centre; Industry Collaboration Award

30 | P a g e Aug 2013 £125,000

Doug Turnbull

NIHR Senior Investigators Award £45,000

Wellcome Trust Wellcome Trust Centre for Mitochondrial Research £4,436,273

Wellcome Trust Wellcome Trust Centre for Mitochondrial Research Public Engagement Enhancement 2014-2017 £286,551

Newcastle University Hospitals NHS Trust RCF - Salary funding for Grainne Gorman 2014-2016 £200,010 e-Therapeutics Collaboration - testing compounds 2013-2014 £112,665

MRC Centre for Ageing and Activity 2014-2019 £2,907,201

MRC Centre for Brain Ageing & Activity Bridging funding 2014 £342,971

Newcastle Healthcare Charity The importance of mitochondrial dysfunction in the pathogenesis of osteoporosis 2013-2016 £157,489

NIHR BRC - Treating mitochondrial dysfunction - mechanisms underlying response to specific compounds 2013-2017 £25,002

Novartis Institutes for BioMedical Research Inc Monogenetic mitochondrial disorders 2013-2017 $100,000

Wellcome Trust

31 | P a g e Eve's Curse: the Art of mitochondrial disease 2013-2014 £7,000

NIHR BRC - NHS Service Support for Mitochondrial theme 2013-2017 £98,428

MRC and BBSRC Centre for Ageing and Vitality (PI and Director) supported by Lifelong Health and Wellbeing 2014-2019 £5.5M

Thomas Voit (PI since 2016)

UCL Therapeutic Innovation Fund and Wellcome Trust Institutional Strategic Support Fund (105604/Z/14/Z) 2016-17 £58K

Tarek Yousry

MRC A next-generation MRI brain imaging platform for dementia research: from microstructure to function 2014 – 2016 £1,217,068

MS Society of GB Imaging research to facilitate treatments for multiple sclerosis April 2013 – March 2018 £1,350,000

MRC MRC Centre for Neuromuscular disease PI for imaging 2013-2017 £3.2M

Wellcome Trust & MRC A systematic investigation into the pathogenesis and course of PD's syndrome 2010-2015 £5.9M

The Stroke Association & BHF Microbleeds and genetic risk factors to predict the risk of intracranial haemorrhage in patients treated with anticoagulation 2010-2015 £939k

32 | P a g e Appendix 4. New publications from Centre since last review

*denotes PI (UCL/NCL) collaboration Bold indicates UCL/NCL PI

Total number of publications: 810 Total number of publications with more than one PI as author: 311

Michael Hanna

1. Rose MR, et al. ENMC International Workshop: Inclusion Body Myositis, 2-4 December 2011, Naarden, The Netherlands. Neuromuscular Disorders. 2013 Dec; 23(12):1044:55. PMID: 24268584

2. Fratta P, Hanna MG, Fisher EM, Sidle K. An unusual presentation for SOD1-ALS: isolated facial diplegia. Muscle Nerve. 2013 Dec;48(6):994-5. PMID: 238735403

3. Cortese A, Plagnol V, Brady S, Simone R, Lashley T, Acevedo-Arozena A, de Silva R, Greensmith L, Holton J, Hanna MG, Fisher EM, Fratta P. Widespread RNA metabolism impairment in sporadic inclusion body myositis TDP43-proteinopathy. Neurobiol Aging. 2013 Dec 30. [Epub ahead of print] PMID: 24462217

4. *Graham CD, Weinman J, Sadjadi R, Chalder T, Petty R, Hanna MG, Turner C, Parton M, Maddison P, Radunovic A, Longman C, Robb Y, Bushby K, Hilton-Jones D, Rose MR. A multicentre postal survey investigating the contribution of illness perceptions, coping and optimism to quality of life and mood in adults with muscle disease. Clin Rehabil. 2013 Nov 15. [Epub ahead of print] PMID: 24240060

5. Machado P, Brady S, Hanna MG. Update in inclusion body myositis. Curr Opin Rheumatol. 2013 Nov;25(6):763-71. PMID: 24067381

6. Jaffer F, Reilly MM, Quinlivan R, Muntoni F, Turner C, Parton M, Lunn M, Hilton-Jones D, Korkodilos M, Hanna MG. Emergency neuromuscular admissions are avoidable: a regional audit of unplanned hospital admissions of neuromuscular patients 2009-2011: final results and recommendations. J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):e2. PMID: 24109054

7. Pitceathly RD, Taanman JW, Rahman S, Meunier B, Sadowski M, Cirak S, Hargreaves I, Land JM, Nanji T, Polke JM, Woodward CE, Sweeney MG, Solanki S, Foley AR, Hurles ME, Stalker J, Blake J, Holton JL, Phadke R, Muntoni F, Reilly MM, Hanna MG. COX10 Mutations Resulting in Complex Multisystem Mitochondrial Disease That Remains Stable Into Adulthood. JAMA Neurol. 2013 Oct 7. [Epub ahead of print] PMID: 24100867

8. Fischmann A, Morrow JM, Sinclair CD, Reilly MM, Hanna MG, Yousry T, Thornton JS. Improved anatomical reproducibility in quantitative lower-limb muscle MRI. J Magn Reson Imaging. 2013 Oct 7. [Epub ahead of print] PMID: 24123788

9.Tan SV, Z'graggen WJ, Boërio D, Rayan DR, Norwood F, Ruddy D, Howard R, Hanna MG, Bostock H. Chloride channels in myotonia congenita assessed by velocity recovery cycles. Muscle Nerve. 2013 Sep 4. [Epub ahead of print] PMID: 24037712.

10. *Fratta P, Collins T, Pemble S, Nethisinghe S, Devoy A, Giunti P, Sweeney MG, Hanna MG, Fisher EM. Sequencing analysis of the spinal bulbar muscular atrophy CAG expansion reveals absence of repeat interruptions. Neurobiol Aging. 2013 Sep 13 [Epub ahead of print] PMID: 24041967

1 | P a g e 11. *Turner C, Hilton-Jones D, Lochmüller H, Hanna MG. MRC Centre for Neuromuscular Diseases 1st (1st December 2010), and 2nd (2nd May 2012) myotonic dystrophy workshops, London, UK and the myotonic dystrophy standards of care and national registry meeting, Newcastle, UK July 2011. Neuromuscul Disord. 2013 Sep 18. [Epub ahead of print] PMID: 24054840

12. Spillane J, Fialho D, Hanna MG. Diagnosis of skeletal muscle channelopathies. Expert Opin Med Diagn. 2013 Sep 26. [Epub ahead of print] PMID: 24066928

13. *Willis TA, Hollingsworth K, Coombs A, Sveen M, Andersen S, Stojkovic T et al. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study, PLoS One, 2013 Aug 14;8(8). PMID: 23967145

14. *Pfeffer G, Horvath R, Klopstock T, Mootha VK, Suomalainen A, Koene S et al. New treatments for mitochondrial disease – no time to drop our standards. Nature Reviews Neurology, July 2013, PMID: 23817350.

15. Ke Q et al. Rare disease centers for periodic paralysis: China vs the US and UK. Muscle Nerve. 2013 July 28. PMID: 23893386

16. *Fratta P, Hanna MG, Fisher EM, Sidle K. An unusual presentation for SOD1- ALS:Isolated facial diplegia. Muscle Nerve. 2013 Jul 19. [Epub ahead of print] PMID: 23873540

17. *Pitceathly RD, Rahman S, Wedatilake Y, Polke JM, Cirak S, Foley AR, Sailer A, Hurles ME, Stalker J, Hargreaves I, Woodward CE, Sweeney MG, Muntoni F, Houlden H, Taanman JW, Hanna MG; UK10K Consortium. NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease. Cell Rep. 2013 Jun 27;3(6):1795-805. Epub 2013 Jun 6. PMID: 23746447

18. Trivedi JR, Bundy B, Statland J, Salajegheh M, Rayan DR, Venance SL, Wang Y, Fialho D, Matthews E, Cleland J, Gorham N, Herbelin L, Cannon S, Amato A, Griggs RC, Hanna MG, Barohn RJ; CINCH Consortium. Non-dystrophic myotonia: prospective study of objective and patient reported outcomes. Brain. 2013 Jul;136(Pt 7):2189-200. Epub 2013 Jun 13. PMID: 23771340

19. *Morrow JM, Matthews E, Raja Rayan DL, Fischmann A, Sinclair CD, Reilly MM, Thornton JS, Hanna MG, Yousry TA. Muscle MRI reveals distinct abnormalities in genetically proven non-dystrophic myotonias. Neuromuscul Disord. 2013 Aug;23(8):637-46. Epub 2013 Jun 27. PMID: 23810313

20. *Morrow JM, Reilly MM, Hanna MG. Reliability and accuracy of skeletal muscle imaging in limb-girdle muscular dystrophies. Neurology. 2013 Jun 11;80(24):2276. PMID: 23905174

21. Wallace A, Dewar E, Skorupinska M, Laura M, Morrow JM, Sterr A, Hanna MG et al. Evaluating the benefits of community based aerobic training on the physical health and well- being of people with neuromuscular diseases: a pilot study. Journal of the Peripheral Nervous System. 18: 123-123. June 2013.

22. Burge JA, Hanna MG, Schorge S. Non-genomic actions of progesterone and 17β- estradiol on the chloride conductance of skeletal muscle. Muscle Nerve. 2013 Apr 26. [Epub ahead of print] PMID: 23625574.

23. Thorne T, Fratta P, Hanna MG, Cortese A, Plagnol V, Fisher EM, Stumpf MP. Graphical modelling of molecular networks underlying sporadic inclusion body myositis. Mol Biosyst. 2013 Apr 17. [Epub ahead of print] PMID: 23595110.

2 | P a g e 24. *Sarkozy A, Hicks D, Hudson J, Laval SH, Barresi R, Hilton-Jones D, et al. ANO5 Gene Analysis in a Large Cohort of Patients with Anoctaminopathy: Confirmation of Male Prevalence and High Occurrence of the Common Exon 5 Gene Mutation. Hum Mutat. 2013 Apr 18. PubMed PMID:23606453.

25. Horga A, Raja Rayan DL, Matthews E, Sud R, Fialho D, Durran SC, Burge JA, Portaro S, Davis MB, Haworth A, Hanna MG. Prevalence study of genetically defined skeletal muscle channelopathies in England. Neurology. 2013 Apr 16;80(16):1472-5. Epub 2013 Mar 20. PMID: 23516313.

26. Cortese A, Machado P, Morrow J, Dewar L, Hiscock A, Miller A, Brady S, Hilton-Jones D, Parton M, Hanna MG. Longitudinal observational study of sporadic inclusion body myositis: Implications for clinical trials. Neuromuscul Disord. 2013 May;23(5):404-12. Epub 2013 Mar 11. PMID: 23489664.

27. Rajakulendran S, Roberts J, Koltzenburg M, Hanna MG, Stewart H. Deletion of chromosome 12q21 affecting KCNC2 and ATXN7L3B in a family with neurodevelopmental delay and ataxia. J Neurol Neurosurg Psychiatry. 2013 Mar 9. [Epub ahead of print] PMID: 23475819.

28. Rajakulendran S, Roberts J, Koltzenburg M, Hanna MG, Stewart H. Deletion of chromosome 12q21 affecting KCNC2 and ATXN7L3B in a family with neurodevelopmental delay and ataxia. J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):1255-7. Epub 2013 Mar 9. PMID: 23475819

29. Malik B, Nirmalananthan N, Gray AL, La Spada AR, Hanna MG, Greensmith L. Co- induction of the heat shock response ameliorates disease progression in a mouse model of human spinal and bulbar muscular atrophy: implications for therapy. Brain. 2013 Mar;136(Pt 3):926-43. Epub 2013 Feb 7. PMID: 23393146

30. Smith MD, Seth JH, Hanna MG, Panicker JN. Detrusor overactivity in Becker muscular dystrophy. Muscle Nerve. 2013 Mar;47(3):464-5. Epub 2013 Feb 4. PMID: 23382079.

31. Tomlinson SE, Rajakulendran S, Tan SV, Graves TD, Bamiou DE, Labrum RW, Burke D, Sue CM, Giunti P, Schorge S, Kullmann DM, Hanna MG. Clinical, genetic, neurophysiological and functional study of new mutations in episodic ataxia type 1. J Neurol Neurosurg Psychiatry. 2013 Jan 24. [Epub ahead of print] PMID: 23349320.

32. *Nesbitt V, Pitceathly RD, Turnbull DM, Taylor RW, Sweeney MG, Mudanohwo EE, Rahman S, Hanna MG, McFarland R. The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation—implications for diagnosis and management. J Neurol Neurosurg Psychiatry. 2013 Jan 25. [Epub ahead of print] PMID: 23355809

33. Portaro S, Musumeci O, Rizzo V, Rodolico C, Buccasfusca M, Toscano A, Sweeney MG, Hanna MG. Stiffness as a presenting symptom of an odd clinical condition caused by multiple sclerosis and myotonia congenita. Neuromuscular Disorders 23(1):52-55 Jan 2013. PMID: 22921319

34. Morrow JM, Matthews E, Raja Rayan D, Fischmann A, Sinclair CDJ, Reilly MM, Thornton JS, Hanna MG, Yousry T. Muscle MRI reveals distinct abnormalities genetically proven non-dystrophic myotonias. Neuromuscular Disorders. 2013. PMID: 23810313

35. Pitceathly RDS, Tomlinson SE, Holton JL, Morrow JM, Rahman S, Hanna MG et al. Distal myopathy with cachexia: an unrecognized phenotype caused by dominantly-inherited mitochondrial polymerase y mutations. JNNP 84(1):107-110. Jan 2013. PMID: 22933815

3 | P a g e 36. *Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmüller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PLoS One. 2013;8(8):e70993. eCollection 2013. PMID: 23967145

37. Machado PM, Ahmed M, Brady S, Gang Q, Healy E, Morrow JM, Wallace AC, Dewar L, Ramdharry G, Parton M, Holton JL, Houlden H, Greensmith L, Hanna MG. Ongoing developments in sporadic inclusion body myositis. Curr Rheumatol Rep. 2014 Dec;16(12):477. PMID: 25399751

38. Corrochano S, Männikkö R, Joyce PI, McGoldrick P, Wettstein J, Lassi G, Raja Rayan DL, Blanco G, Quinn C, Liavas A, Lionikas A, Amior N, Dick J, Healy EG, Stewart M, Carter S, Hutchinson M, Bentley L, Fratta P, Cortese A, Cox R, Brown SD, Tucci V, Wackerhage H, Amato AA, Greensmith L, Koltzenburg M, Hanna MG, Acevedo-Arozena A. Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis. Brain. 2014 Dec;137(Pt 12):3171-85. PMID: 25348630

39. *Horga A, Pitceathly RD, Blake JC, Woodward CE, Zapater P, Fratter C, Mudanohwo EE, Plant GT, Houlden H, Sweeney MG, Hanna MG, Reilly MM. Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia. Brain. 2014 Dec;137(Pt 12):3200-12. PMID: 25281868

40. *Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzińska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Am J Hum Genet. 2014 Nov 6;95(5):590-601. PMID: 25439726

41. Singh RR, Tan SV, Hanna MG, Robb SA, Clarke A, Jungbluth H. Mutations in SCN4A: a rare but treatable cause of recurrent life-threatening laryngospasm. Pediatrics. 2014 Nov;134(5):e1447-50. PMID: 25311598.

42. Matthews E, Hanna MG. Repurposing of sodium channel antagonists as potential new anti-myotonic drugs. Exp Neurol. 2014 Nov;261:812-5. PMID: 25218042.

43. Suetterlin K, Männikkö R, Hanna MG. Muscle channelopathies: recent advances in genetics, pathophysiology and therapy. Curr Opin Neurol. 2014 Oct;27(5):583-90. PMID: 25188014.

44. Quinlivan R, Matthews E, Hanna MG. Innovative care model for patients with complex muscle diseases. Curr Opin Neurol. 2014 Oct;27(5):607-13. PMID: 25188015.

45. Gang Q, Bettencourt C, Machado P, Hanna MG, Houlden H. Sporadic inclusion body myositis: the genetic contributions to the pathogenesis. Orphanet J Rare Dis. 2014 Jun 19;9:88. Review. PubMed PMID: 24948216

46. Montague K, Malik B, Gray AL, La Spada AR, Hanna MG, Szabadkai G, Greensmith L. Endoplasmic reticulum stress in spinal and bulbar muscular atrophy: a potential target for therapy. Brain. 2014 Jul;137(Pt 7):1894-906. Epub 2014 Jun 4. PMID: 24898351

47. Fratta P, Nirmalananthan N, Masset L, Skorupinska I, Collins T, Cortese A, Pemble S, Malaspina A, Fisher EM, Greensmith L, Hanna MG. Correlation of clinical and molecular

4 | P a g e features in spinal bulbar muscular atrophy. Neurology. 2014 May 9. [Epub ahead of print] PMID: 24814851

Birbeck GL, Hanna MG, Griggs RC. Global opportunities and challenges for clinical neuroscience. JAMA. 2014 Apr 23-30;311(16):1609-10. PMID: 24756506

48. Morrow JM, Sinclair CD, Fischmann A, Reilly MM, Hanna MG, Yousry TA, Thornton JS. Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers. Eur Radiol. 2014 Apr 20. [Epub ahead of print] PMID: 24748539

49. Foley AR, Pitceathly RD, He J, Kim J, Pearson NM, Muntoni F, Hanna MG. Whole- genome sequencing and the clinician: a tale of two cities. J Neurol Neurosurg Psychiatry. 2014 Apr 4.[Epub ahead of print] PMID: 24706943

50. Graves TD, Cha YH, Hahn AF, Barohn R, Salajegheh MK, Griggs RC, Bundy BN, Jen JC, Baloh RW, Hanna MG; CINCH Investigators. Episodic ataxia type 1: clinical characterization, quality of life and genotype-phenotype correlation. Brain. 2014 Apr;137(Pt 4):1009-18. Epub 2014 Feb 26. PMID: 24578548

51. *Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmuller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross- sectional study. PLoS One. 2014 Feb 28;9(2) PMID: 24587344

52. Habbout K, Poulin H, Rivier F, Giuliano S, Sternberg D, Fontaine B, Eymard B,Morales RJ, Echenne B, King L, Hanna MG, Männikkö R, Chahine M, Nicole S,Bendahhou S. A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis. Neurology. 2016 Jan 12;86(2):161-9. Epub 2015 Dec 11. PubMed PMID: 26659129

53. Suetterlin KJ, Bugiardini E, Kaski JP, Morrow JM, Matthews E, Hanna MG, Fialho D. Long-term Safety and Efficacy of Mexiletine for Patients With Skeletal Muscle Channelopathies. JAMA Neurol. 2015 Dec;72(12):1531-3. PubMed PMID: 26658970.

54. Poole OV, Hanna MG, Pitceathly RD. Mitochondrial disorders: disease mechanisms and therapeutic approaches. Discov Med. 2015 Nov;20(111):325-31. PubMed PMID: 26645904.

55. Gang Q, Bettencourt C, Houlden H, Hanna MG, Machado PM. Genetic advances in sporadic inclusion body myositis. Curr Opin Rheumatol. 2015 Nov;27(6):586-94. Review. PubMed PMID: 26335925.

56. Spillane J, Kullmann DM, Hanna MG. Genetic neurological channelopathies:molecular genetics and clinical phenotypes. J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):37-48. Epub 2015 Nov 11. Review. PubMed PMID: 26558925

57. Morrow JM, Sinclair CD, Fischmann A, Machado PM, Reilly MM, Yousry TA,Thornton JS, Hanna MG. MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study. Lancet Neurol. 2016 Jan;15(1):65-77. Epub 2015 Nov 6. PubMed PMID: 26549782

58. Rothwell S, Cooper RG, Lundberg IE, Miller FW, Gregersen PK, Bowes J,Vencovsky J, Danko K, Limaye V, Selva-O'Callaghan A, Hanna MG, Machado PM, Pachman LM, Reed AM, Rider LG, Cobb J, Platt H, Molberg Ø, Benveniste O, Mathiesen P, Radstake T, Doria A, De Bleecker J, De Paepe B, Maurer B, Ollier WE, Padyukov L, O'Hanlon TP, Lee A, Amos CI, Gieger C, Meitinger T, Winkelmann J, Wedderburn LR, Chinoy H, Lamb JA;

5 | P a g e Myositis Genetics Consortium. Dense genotyping of immune-related loci in idiopathic inflammatory myopathies confirms HLA alleles as the strongest genetic risk factor and suggests different genetic background for major clinical subgroups. Ann Rheum Dis. 2016 Aug;75(8):1558-66. Epub 2015 Sep 11. PubMed PMID: 26362759.

59. Gilbert JR, Symmonds M, Hanna MG, Dolan RJ, Friston KJ, Moran RJ. Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations. Neuroimage. 2016 Jan 1;124(Pt A):43-53. Epub 2015 Sep 3. PubMed PMID: 26342528

60. Jaffer F, Avbersek A, Vavassori R, Fons C, Campistol J, Stagnaro M, De Grandis E, Veneselli E, Rosewich H, Gianotta M, Zucca C, Ragona F, Granata T, Nardocci N, Mikati M, Helseth AR, Boelman C, Minassian BA, Johns S, Garry SI, Scheffer IE, Gourfinkel-An I, Carrilho I, Aylett SE, Parton M, Hanna MG, Houlden H, Neville B, Kurian MA, Novy J, Sander JW, Lambiase PD, Behr ER, Schyns T, Arzimanoglou A, Cross JH, Kaski JP, Sisodiya SM. Faulty cardiac repolarization reserve in alternating hemiplegia of childhood broadens the phenotype. Brain. 2015 Oct;138(Pt 10):2859-74. Epub 2015 Aug 21. PubMed PMID: 26297560.

61. *Figueroa-Bonaparte S, Hudson J, Barresi R, Polvikoski T, Williams T, Töpf A, Harris E, Hilton-Jones D, Petty R, Willis TA, Longman C, Dougan CF, Parton MJ,Hanna MG, Quinlivan R, Farrugia ME, Guglieri M, Bushby K, Straub V, Lochmüller H, Evangelista T. Mutational spectrum and phenotypic variability of VCP-related neurological disease in the UK. J Neurol Neurosurg Psychiatry. 2016 Jun;87(6):680-1. Epub 2015 Jun 23. PubMed PMID: 26105173

62. Broomfield A, Sweeney MG, Woodward CE, Fratter C, Morris AM, Leonard JV, Abulhoul L, Grunewald S, Clayton PT, Hanna MG, Poulton J, Rahman S. Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease. J Inherit Metab Dis. 2015 May;38(3):445-57 PMID: 25352051

63. Sewry CA, Holton JL, Dick DJ, Muntoni F, Hanna MG. Zebra body myopathy is caused by a mutation in the skeletal muscle actin gene (ACTA1). Neuromuscul Disord. 2015 May;25(5):388-91. PMID: 25747004.

64. Pitceathly RD, Morrow JM, Sinclair CD, Woodward C, Sweeney MG, Rahman S, Plant GT, Ali N, Bremner F, Davagnanam I, Yousry TA, Hanna MG, Thornton JS. Extra-ocular muscle MRI in genetically-defined mitochondrial disease. Eur Radiol. 2015 May 21. [Epub ahead of print] PMID: 25994195.

65. Gang Q, Bettencourt C, Machado PM, Fox Z, Brady S, Healy E, Parton M, Holton JL, Hilton-Jones D, Shieh PB, Zanoteli E, De Paepe B, De Bleecker J, Shaibani A, Ripolone M, Violano R, Moggio M, Barohn RJ, Dimachkie MM, Mora M, Mantegazza R, Zanotti S, Hanna MG, Houlden H; Muscle Study Group and the International IBM Genetics Consortium. The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis. Neurobiol Aging. 2015 Apr;36(4):1766.e1-3. PMID: 25670332

66. *Hall AM, Vilasi A, Garcia-Perez I, Lapsley M, Alston CL, Pitceathly RD, McFarland R, Schaefer AM, Turnbull DM, Beaumont NJ, Hsuan JJ, Cutillas PR, Lindon JC, Holmes E, Unwin RJ, Taylor RW, Gorman GS, Rahman S, Hanna MG. The urinary proteome and metabonome differ from normal in adults with mitochondrial disease. Kidney Int. 2015 Mar;87(3):610-22. PMID: 25207879.

67. Herbert MK, Stammen-Vogelzangs J, Verbeek MM, Rietveld A, Lundberg IE, Chinoy H, Lamb JA, Cooper RG, Roberts M, Badrising UA, De Bleecker JL, Machado PM, Hanna MG, Plestilova L, Vencovsky J, van Engelen BG, Pruijn GJ. Disease specificity of autoantibodies to cytosolic 5'-nucleotidase 1A in sporadic inclusion body myositis versus known

6 | P a g e autoimmune diseases. Ann Rheum Dis. 2015 Feb 24. pii: annrheumdis-2014-206691. PMID: 25714931.

68. Fratta P, Hanna MG. Neuromuscular diseases: progress in gene discovery drives diagnostics and therapeutics. Lancet Neurol. 2015 Jan;14(1):13-4. PMID: 25496885.

69. Akman G, Desai R, Bailey LJ, Yasukawa T, Dalla Rosa I, Durigon R, Holmes JB, Moss CF, Mennuni M, Houlden H, Crouch RJ, Hanna MG, Pitceathly RD, Spinazzola A, Holt IJ. Pathological ribonuclease H1 causes R-loop depletion and aberrant DNA segregation in mitochondria. Proc Natl Acad Sci U S A. 2016 Jul 8. [Epub ahead of print] PubMed PMID: 27402764.

70. Mestre TA, Manole A, MacDonald H, Riazi S, Kraeva N, Hanna MG, Lang AE, Männikkö R, Yoon G. A novel KCNA1 mutation in a family with episodic ataxia and malignant hyperthermia. Neurogenetics. 2016 Jun 8. [Epub ahead of print] PubMed PMID: 27271339.

71. Bertolin C, Querin G, Da Re E, Sagnelli A, Bello L, Cao M, Muscas M, Pennuto M, Ermani M, Pegoraro E, Mariotti C, Gellera C, Hanna MG, Pareyson D, Fratta P,Sorarù G. No effect of AR polyG polymorphism on spinal and bulbar muscular atrophy phenotype. Eur J Neurol. 2016 Jun;23(6):1134-6. PMID: 27141859.

72. *Scalco RS, Gardiner AR, Pitceathly RD, Hilton-Jones D, Schapira AH, Turner C, Parton M, Desikan M, Barresi R, Marsh J, Manzur AY, Childs AM, Feng L, Murphy E, Lamont PJ, Ravenscroft G, Wallefeld W, Davis MR, Laing NG, Holton JL, Fialho D, Bushby K, Hanna MG, Phadke R, Jungbluth H, Houlden H, Quinlivan R. CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies. Neuromuscul Disord. 2016 May 11. [Epub ahead of print] PubMed PMID: 27312022.

73. Tan SV, Z'graggen WJ, Boërio D, Turner C, Hanna MG, Bostock H. In vivoassessment of muscle membrane properties in myotonic dystrophy. Muscle Nerve. 2016 Aug;54(2):249- 57. Epub 2016 May 24. PubMed PMID: 26789642.

74. Ahmed M, Machado PM, Miller A, Spicer C, Herbelin L, He J, Noel J, Wang Y, McVey AL, Pasnoor M, Gallagher P, Statland J, Lu CH, Kalmar B, Brady S, Sethi H, Samandouras G, Parton M, Holton JL, Weston A, Collinson L, Taylor JP, Schiavo G, Hanna MG, Barohn RJ, Dimachkie MM, Greensmith L. Targeting protein homeostasis in sporadic inclusion body myositis. Sci Transl Med. 2016 Mar 23;8(331):331ra41. PubMed PMID: 27009270.

75. Hanna MG, Pantanowitz L. Bar Coding and Tracking in Pathology. Clin Lab Med. 2016 Mar;36(1):13-30. Review. PubMed PMID:26851661.

76. Tomlinson SE, Tan SV, Burke D, Labrum RW, Haworth A, Gibbons VS, Sweeney MG, Griggs RC, Kullmann DM, Bostock H, Hanna MG. In vivo impact of presynaptic calcium channel dysfunction on motor axons in episodic ataxia type 2. Brain. 2016 Feb;139(Pt 2):380-91. PubMed PMID: 26912519.

77. Sansone VA, Burge J, McDermott MP, Smith PC, Herr B, Tawil R, Pandya S, Kissel J, Ciafaloni E, Shieh P, Ralph JW, Amato A, Cannon SC, Trivedi J, Barohn R, Crum B, Mitsumoto H, Pestronk A, Meola G, Conwit R, Hanna MG, Griggs RC; Muscle Study Group. Randomized, placebo-controlled trials of dichlorphenamide in periodic paralysis. Neurology. 2016 Apr 12;86(15):1408-16. Epub 2016 Feb 10. PubMed PMID: 26865514.

78. Rajakulendran S, Pitceathly RD, Taanman JW, Costello H, Sweeney MG, Woodward CE, Jaunmuktane Z, Holton JL, Jacques TS, Harding BN, Fratter C, Hanna MG, Rahman S. A Clinical, Neuropathological and Genetic Study of Homozygous A467T POLG-Related

7 | P a g e Mitochondrial Disease. PLoS One. 2016 Jan 6;11(1):e0145500. eCollection 2016. PubMed PMID: 26735972

79. Rajakulendran S, Hanna MG. The Role of Calcium Channels in Epilepsy. ColdSpring Harb Perspect Med. 2016 Jan 4;6(1):a022723. Review. PubMed PMID: 26729757.

80. Zaharieva IT, Thor MG, Oates EC, van Karnebeek C, Hendson G, Blom E, Witting N, Rasmussen M, Gabbett MT, Ravenscroft G, Sframeli M, Suetterlin K, Sarkozy A, D'Argenzio L, Hartley L, Matthews E, Pitt M, Vissing J, Ballegaard M, Krarup C, Slørdahl A, Halvorsen H, Ye XC, Zhang LH, Løkken N, Werlauff U, Abdelsayed M, Davis MR, Feng L, Phadke R, Sewry CA, Morgan JE, Laing NG, Vallance H, Ruben P, Hanna MG, Lewis S, Kamsteeg EJ, Männikkö R, Muntoni F. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy. Brain. 2016 Mar;139(Pt 3):674-91. Epub 2015 Dec 22. PubMed PMID: 26700687.

Gang Q, Bettencourt C, Machado PM, Brady S, Holton JL, Pittman AM, Hughes D7 Healy E, Parton M, Hilton-Jones D, Shieh PB, Needham M, Liang C, Zanoteli E, de Camargo LV, De Paepe B, De Bleecker J, Shaibani A, Ripolone M, Violano R, Moggio M, Barohn RJ, Dimachkie MM, Mora M, Mantegazza R, Zanotti S, Singleton AB, Hanna MG, Houlden H; Muscle Study Group and The International IBM Genetics Consortium. Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis. Neurobiol Aging. 2016 Aug 8. pii: S0197-4580(16)30161-0. PMID: 27594680.

Mary M. Reilly

81. Mead S, Gandhi S, Beck J, Caine D, Gallujipali D, Carswell C, Hyare H, Joiner S, Ayling H, Lashley T, Linehan JM, Al-Doujaily H, Sharps B, Revesz T, Malin MD, Sandberg K, Reilly MM, Koltzenburg M, Forbes A, Rudge P, Brandner S, Warren JD, Wadsworth JDF, Wood NW, Holton JL, and Collinge J, M.D. A Novel Disease Associated with Diarrhoea and Autonomic Neuropathy. N Engl J Med 2013;369:1904 -14. PMID: 24224623

82. Sumner CJ, d’Ydewalle, C, Wooley J, Fawcett, KA, Hernandez D, Gardiner AR, Kalmar B, Baloh RH, Gonzalez M, Zuchner S, Stanescu CH, Kleta R, Mankodi A, Cornblath DR, Boylan KB, Reilly MM, Greensmith L, Singleton AB, Harms MB, Rossor AM, and Houlden H*. A Dominant Mutation in FBXO38 Causes Distal Spinal Muscular Atrophy with Calf Predominance. American Journal of Human Genetics 93, 976–983, November 7, 2013. PMID: 24207122

83. Liu Y-T, Hersheson J, Plagnol V, Fawcett K, Duberley KEC, Preza E, Hargreaves IA, Chalasani A, Laurá M, Wood NW, Reilly MM, Houlden H. Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation. J Neurol Neurosurg Psychiatry November 11, 2013 as 10.1136/jnnp-2013-306483. PMID: 24218524

84. Tucci A, Liu Y-T, Preza E, Pitceathly RDS, Chalasani A, Plagnol V, Land JM, Trabzun Di, Ryten M, on behalf of UKBEC, Jaunmuktane Z, Reilly MM, Brandner S, Hargreaves I, Hardy J, Singleton A, Abramov AY, Houlden H. Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy. J Neurol Neurosurg Psychiatry November 6, 2013 as 10.1136/jnnp-2013-306387. PMID: 24198383

85. Jaffer F, Reilly MM, Quinlivan R, Muntoni F, Turner C, Parton M, Lunn M, Hilton-Jones D, Korkodilos M, Hanna MG. Emergency neuromuscular admissions are avoidable: A regional audit of unplanned hospital admissions of neuromuscular patients 2009-11: final results and recommendations J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):e2.

8 | P a g e 86. Pitceathly RD, Taanman JW, Rahman S, Meunier B, Sadowski M, Cirak S, Hargreaves I, Land JM, Nanji T, Polke JM, Woodward CE, Sweeney MG, Solanki S, Foley AR, Hurles ME, Stalker J, Blake J, Holton JL, Phadke R, Muntoni F, Reilly MM, Hanna MG; COX10 Mutations Resulting in Complex Multisystem mitochondrial Disease That Remains Stable Into Adulthood. UK10K Consortium.JAMA Neurol. 2013 Oct 7. PMID: 24100867

87. Rossor AM, Polke JM, Houlden H, Reilly MM. Clinical implications of genetic advances in Charcot-Marie-Tooth disease.Nat Rev Neurol. 2013 Oct;9(10):562-571. PMID: 24018473

88. Murphy SM, Laurá M, Reilly MM. DNA testing in hereditary neuropathies. Handb Clin Neurol. 2013;115:213-32. PMID: 23931782

89. Oates EC, Rossor AM, Hafezparast M, Gonzalez M, Speziani F, Macarthur DG, Lek M, Cottenie E, Scoto M, Foley AR, Hurles M, Houlden H, Greensmith L, Auer-Grumbach M, Pieber TR, Strom TM, Schule R, Herrmann DN, Sowden JE, Acsadi G, Menezes MP, Clarke NF, Züchner S; UK10K, Muntoni F, North KN, Reilly MM. Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia. Am J Hum Genet. 2013: 92; 1-9. PMID: 23664120

90. Gonzalez M, McLaughlin H, Houlden H, Guo M, Yo-Tsen L, Hadjivassilious M, Speziani F, Yang XL, Antonellis A, Reilly MM, Züchner S; Inherited Neuropathy Consortium (INC). Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2. J Neurol Neurosurg Psychiatry. 2013 Jun 1. [Epub ahead of print] PMID: 23729695

91. Morrow JM, Matthews E, Raja Rayan DL, Fischmann A, Sinclair CD, Reilly MM, Thornton JS, Hanna MG, Yousry TA. Muscle MRI reveals distinct abnormalities in genetically proven non-dystrophic myotonias. Neuromuscul Disord. 2013 Jun 26 [Epub ahead of print] PMID: 23810313

92. Reilly MM. Obstructive sleep apnoea, restless leg syndrome and Charcot-Marie-Tooth disease type 1: important associations. J Neurol Neurosurg Psychiatry. 2013 Jun 11. [Epub ahead of print] PMID: 23757421

93. Morrow JM, Reilly MM, Hanna MG. Reliability and accuracy of skeletal muscle imaging in limb-girdle muscular dystrophies. Neurology. 2013: 80; 2276. PMID: 23905174

94. Marquez-Infante C, Murphy SM, Mathew L, Alsanousi A, Lunn MP, Brandner S, Yousry TA, Blake J, Reilly MM. Asymmetric sensory ganglionopathy: A case series. Muscle Nerve. 2013 Jul;48(1):145-50. PMID: 23744601

95. Dujmovic I, Lunn MP, Reilly MM, Petzold A. Serial cerebrospinal fluid neurofilament heavy chain levels in severe Guillain-Barré syndrome. Muscle Nerve. 2013 Jul; 48(1):132-4. PMID: 23716297

96. Schwingenschuh P, Saifee TA, Katschnig-Winter P, Reilly MM, Lunn MP, Manji H, Aguirregomozcorta M, Schmidt R, Bhatia KP, Rothwell JC, Edwards MJ. Cerebellar learning distinguishes inflammatory neuropathy with and without tremor. Neurology. 2013 May 14;80(20):1867-73. PMID: 23596070

97. Visioli F, Reilly MM, Rimoldi M, Solari A, Pareyson D; for the CMT-TRIAAL & CMT- TRAUK Groups. Vitamin C and Charcot-Marie-Tooth 1A: Pharmacokinetic considerations. PharmaNutrition. 2013 Jan;1(1):10-12. PMID: 23525455

98. Cottenie E, Menezes MP, Rossor AM, Morrow JM, Yousry TA, Dick DJ, Anderson JR, Jaunmuktane Z, Brandner S, Blake JC, Houlden H, Reilly MM. Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic

9 | P a g e inflammatory demyelinating polyneuropathy . Neuromuscul Disord. 2013 May;23(5):399-403. PMID: 23489662

99. Koutsis G, Pandraud A, Reilly MM, Wood, NW, Houlden H, Karadima G, Floroskufi P, (2013). Mutational analysis of PMP22, EGR2, LITAF and NEFL in Greek Charcot-Marie- Tooth type 1 patients. Clinical Genetics, 83(4), 388-391. PMID: 22765307

100. Murphy SM, Ernst D, Wei Y, Laurà M, Liu YT, Polke J, Blake J, Winer J, Houlden H, Hornemann T, Reilly MM. Hereditary sensory and autonomic neuropathy type 1 (HSANI) caused by a novel mutation in SPTLC2. Neurology. 2013 Jun 4;80(23):2106-2111. PMID: 23658386

101. Burns J, Menezes M, Finkel RS, Estilow T, Moroni I, Pagliano E, Laurá M, Muntoni F, Herrmann DN, Eichinger K, Shy R, Pareyson D, Reilly MM, Shy ME. Transitioning outcomes measures: Relationship between the CMTPedS and CMTNSv2 in children, adolescents and young adults with Charcot-Marie-Tooth disease. Journal of the Peripheral Nervous System 2013: 18; 177-180. PMID: 23781965

102. Stevens JC, Murphy SM, Davagnanam I, Phadke R, Anderson G, Nethisinghe S, Bremner F, Giunti P, Reilly MM. The ARSACS phenotype can include supranuclear gaze palsy and lipofuscin skin deposits. JNNP 2013: 84; 114-116. PMID: 23123642

103. Mannil M, Solari A, Leha A, Pelayo-Negro AL, Berciano J, Schlotter-Weigel, B, Reilly MM, Sereda M W (2014). Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patient. Neuromuscul Disord. PMID: 25085517

104. Neligan A, Reilly MM,& Lunn MP, (2014). CIDP: mimics and chameleons. Pract Neurol. PMID:25035142

105. Liu Y T, Laurá M, Hersheson J, Horga A, Jaunmuktane Z, Brandner S, Reilly MM, Houlden H. (2014). Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. Neurology. PMID: 25008398

106. Morrow JM, Sinclair CDJ, Fischmann A, Reilly MM, Hanna MG, Yousry TA, Thornton JS. (2014). Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers. European Radiology, 24(7), 1610-1620. PMID: 24748539

107. Nobbio L, Visigalli D, Radice D, Fiorina E, Solari A, Lauria, G, Reilly MM, CMT-TRIAAL Group.(2014). PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker.. Brain, 137(Pt 6), 1614-1620. PMID: 24812204

108. Brewer MH, Ma KH, Beecham GW, Reilly MM, Gopinath C, the Inherited Neuropath Consortium (INC), Baas F, Antonellis A. (2014). Haplotype-Specific Modulation of a SOX10/CREB Response Element at the Charcot-Marie-Tooth Disease Type 4C Locus SH3TC2. HuMMol Genet. PMID: 24883716

109. Laurà M, PhD 1, Hutton E, Blake J, Lunn M P, Fox Z, Pareyson D, Solari A, Radice D, Koltzenburg M, Reilly MM. Pain and small fiber function in Charcot Marie Tooth disease type 1A. Muscle Nerve Jan 2014 PMID: 24395492

110. *Foley AR, Menezes MP, Pandraud A, Gonzalez MA, Al-Odaib A, Abrams AJ, Sugano K, Yonezawa A, Manzur AY, Burns J, Hughes I, McCullagh BG, Jungbluth H, Lim MJ, Lin JP, Megarbane A, Urtizberea JA, Shah AH, Antony J, Webster R, Broomfield A, Ng J, Mathew AA, O'Byrne JJ, Forman E, Scoto M, Prasad M, O'Brien K, Olpin S, Oppenheim M,

10 | P a g e Hargreaves I, Land JM, Wang MX, Carpenter K, Horvath R, Straub V, Lek M, Gold W, Farrell MO, Brandner S, Phadke R, Matsubara K, McGarvey ML, Scherer SS, Baxter PS, King MD, Clayton P, Rahman S, Reilly MM, Ouvrier RA, Christodoulou J, Züchner S, Muntoni F, Houlden H, Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain 2014: 137; 44–56 PMID: 24253200

111. Piscosquito G, Reilly MM, Schenone A et al. Is overwork weakness relevant in Charcot–Marie–Tooth disease? J Neurol Neurosurg Psychiatry March 21, 2014 as 10.1136/jnnp-2014-307598. PMID: 24659785

112. Schabhűtt lM, Wieland M, Senderek, Baets J, Timmerman V, De Jonghe P, Reilly MM, Stieglbauer K, Laich E, Windhager R, Erwa W, Trajanoski S, Strom T M, Auer-Grumbach M. Whole-exome sequencing in patients with inherited neuropathies: outcome and challenges. J Neurol March 15, 2014. PMID: 24627108

113. Fischmann A, Morrow JM, Sinclair CDJ, Reilly MM, Hanna MG, Yousry T, and Thornton JS. Improved Anatomical Reproducibility in Quantitative Lower-Limb Muscle MRI. J Magn Reson Imaging 2014; 39: 1033-8. PMID: 24123788

114. Evans MR, Laurá M, Chandrashekar H, Reilly MM. Cervical spinal cord compression complicating the clinical course of Charcot-Marie-Tooth type 1. BMJ Case Rep. 2015 Dec 17;2015. pii: bcr2015213486. PMID: 26678696.

115. Gess B, Baets J, De Jonghe P, Reilly MM, Pareyson D, Young P. Ascorbic acid for the treatment of Charcot-Marie-Tooth disease. Cochrane Database Syst Rev. 2015 Dec 11;12:CD011952. Review. PMID: 26662471.

116. Morrow JM, Sinclair CD, Fischmann A, Machado PM, Reilly MM, Yousry TA, Thornton JS, Hanna MG. MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study. Lancet Neurol. 2016 Jan;15(1):65-77. Epub 2015 Nov 6. PubMed PMID: 26549782

117. Vanhoutte EK, Faber CG, van Nes SI, Cats EA, Van der Pol WL, Gorson KC, van Doorn PA, Cornblath DR, van den Berg LH, Merkies IS; PeriNomS Study Group. Rasch-built Overall Disability Scale for Multifocal motor neuropathy (MMN-RODS(©). J Peripher Nerv Syst. 2015 Sep;20(3):296-305. PMID: 26329270.

118. Sanmaneechai O, Feely S, Scherer SS, Herrmann DN, Burns J, Muntoni F, Li J, Siskind CE, Day JW, Laura M, Sumner CJ, Lloyd TE, Ramchandren S, Shy RR, Grider T, Bacon C, Finkel RS, Yum SW, Moroni I, Piscosquito G, Pareyson D, Reilly MM, Shy ME; Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC- RDCRC). Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene. Brain. 2015 Nov;138(Pt 11):3180-92. Epub 2015 Aug 25. PMID: 26310628; PubMed Central PMCID: PMC4643641.

119. Fridman V, Reilly MM. Inherited Neuropathies. Semin Neurol. 2015 Aug;35(4):407-23. Epub 2015 Oct 6. PMID: 26502764

120. Sanmaneechai O, Feely S, Scherer SS, Herrmann DN, Burns J, Muntoni F, Li J, Siskind CE, Day JW, Laura M, Sumner CJ, Lloyd TE,, Ramchandren S, Shy RR2, Grider T, Bacon C, Finkel RS, Yum SW, Moroni I, Piscosquito G, Pareyson D, Reilly MM, Shy ME. Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene. Brain : Aug 2015 (Epub ahead of print).PMID: 26310628

11 | P a g e 121. Koutsis G, Lynch D, Manole A, Karadima G, Reilly MM, Houlden H, Panas M. Erratum to: Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome in a patient with the R232C TRPV4 mutation. J Neurol. 2015 Aug;262(8):1976. PMID: 26162716

122. Carr AS, Polke JM, Wilson J, Pelayo-Negro AL, Laura M, Nanji T, Holt J, Vaughan J, Rankin J, Sweeney MG, Blake J, Houlden H, Reilly MM.(2015). MFN2 deletion of exons 7 and 8: founder mutation in the UK population. Journal of the peripheral nervous system: JPNS. PMID: 26114802

123. Horga A, Cottenie E, Tomaselli P J, Rojas-García R, Salvado M, Villarreal-Pérez L L, Gamez J, Márquez-Infante C, Houlden H, Reilly MM. (2015). Absence of HINT1 mutations in a UK and Spanish cohort of patients with inherited neuropathies. Journal of neurology. PMID: 26194197

124. Piscosquito G, Reilly MM, Schenone A, Fabrizi GM, Cavallaro T, Santoro L, Manganelli F, Vita G, Quattrone A, Padua L, Gemignani F, Visioli F, Laurà M, Calabrese D, Hughes RA, Radice D, Solari A, Pareyson D; CMT-TRIAAL and CMT-TRAUK Group. Responsiveness of clinical outcome measures in Charcot-Marie-Tooth disease.Eur J Neurol. 2015 Jul 31. PMID: 26227902

125. Carr AS, Pelayo-Negro A L, Evans MR, Laurà M, Blake J, Stancanelli C, Iodice V, Wechalekar AD, Whelan CJ, Gilmore JD, Hawkins PN, Reilly MM. (2015). A study of the neuropathy associated with transthyretin amyloidosis (ATTR) in the UK. Journal of neurology, neurosurgery, and psychiatry. PMID: 26243339

126. Chen YC, Auer-Grumbach M, Matsukawa S, Zitzelsberger M, Themistocleous A C, Strom TM, Samara C, Samara C, Moore AW, Cho LT, Young GT, Weiss C, Schabhüttl M, Stucka R, Schmid AB, Parman Y, Graul-Neumann L, Heinritz W, Passarge E, Watson RM, Hertz JM, Moog U, Baumgartner M, Valente EM, Pereira D, Restrepo CM, Katona I, Dusl M, Stendel C, Wieland T, Stafford F, Reimann F, von Au K, Finke C, Willems PJ, Nahorski MS, Shaikh SS, Carvalho OP, Nicholas AK, Karbani G, McAleer MA, Cilio MR, McHugh JC, Murphy SM, Irvine AD, Jensen UB, Windhager R, Weis J, Bergmann C, Rautenstrauss B, Baets J, De Jonghe P, Reilly MM, Kropatsch R, Kurth I, Chrast R, Michiue T, Bennett DL, Woods CG, Senderek J. (2015). Transcriptional regulator PRDM12 is essential for human pain perception. Nature genetics. PMID: 26005867

127. Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzales MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN.(2015). Reply: The .Ser107Leu in BICD2 is a mutation 'hot spot' causing distal spinal muscular atrophy. Brain: a journal of neurology. PMID: 26063657

128. Koutsis G, Lynch D, Manone A, Karadima G, Reilly MM, Houlden H, Panas M. (2015). Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome in a patient with the R232C TRPV4 mutation. Journal of Neurology.Jun 6 (Epub ahead of print) PMID: 26048687

129. Healy EG, Phadke R, Kidd M, Reilly MM, Lunn MP. Clinical, neuropathological and radiological evidence for a rare complication of rituximab therapy. Neuromuscul Disord. 2015 Apr 16. pii: S0960-8966(15)00129-7. PMID: 25958339

130. Rossor AM, Evans MR, & Reilly, MM. (2015). A practical approach to the genetic neuropathies. Practical neurology. PMID: 25898997

12 | P a g e 131. Carr AS, Pelayo-Negro AL, Jaunmuktane Z, Scalco RS, Evans MRB, Healy E, Brandner S, Holton J, Blake J, Whelan CJ, Wechalekar AD, Gillmore JD, Hawkins PN, Reilly MM. M.,.Hawkins, P. N. Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy. 2015. Neuromuscular Disorders. PMID: 25819286

132. Morrow JM, & Reilly MM. Early detection of nerve injury in transthyretin-related Familial amyloid polyneuropathy. 2015. Brain: a journal of neurology, 138(Pt 3), 507-509. PMID: 25713400

133. Scoto M, Rossor AM, Harms MB, Cirak S, Calissano M, Robb S, Manzur AY, Martínez Arroyo A, Rodriguez Sanz A, Mansour S, Fallon P, Hadjikoumi I, Klein A, Yang M, De Visser M, Overweg-Plandsoen WC, Baas F, Taylor JP, Benatar M, Connolly AM, Al-Lozi MT, Nixon J, de Goede CG, Foley AR, Mcwilliam C, Pitt M, Sewry C, Phadke R, Hafezparast M, Chong WK, Mercuri E, Baloh RH, Reilly MM, Muntoni F. Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy. Neurology 84(7):668-679 17 Feb 2015 (Journal article) PMID: 25609763

134. Cornett KM, Menezes MP, Bray P, Halaki M, Shy RR, Yum SW, Estilow T, Moroni I, Foscan M, Pagliano E, Pareyson D, Laurá M, Bhandari T, Muntoni F, Reilly MM, Finkel RS, Sowden J, Eichinger KJ, Herrmann DN, Shy ME, Burns J; Inherited Neuropathies Consortium. Phenotypic Variability of Childhood Charcot-Marie-Tooth Disease. JAMA Neurol. 2016 Apr 4. [Epub ahead of print] PubMed PMID: 27043305.

135. Rebelo AP, Abrams AJ, Cottenie E, Horga A, Gonzalez M, Bis DM, Sanchez-Mejias A, Pinto M, Buglo E, Markel K, Prince J, Laura M, Houlden H, Blake J, Woodward C, Sweeney MG, Holton JL, Hanna M, Dallman JE, Auer-Grumbach M, Reilly MM, Zuchner S. Cryptic Amyloidogenic Elements in the 3' UTRs of Neurofilament Genes Trigger Axonal Neuropathy. Am J Hum Genet. 2016 Apr 7;98(4):597-614. Epub 2016 Mar 31. PubMed PMID: 27040688

136. Reilly MM. Untreatable genetic disorders: to test or not to test. Pract Neurol. 2016 Jun;16(3):174-5.. Epub 2016 Mar 25. PubMed PMID: 27016509.

137. Rossor AM, Liu CH, Petzold A, Malaspina A, Laura M, Greensmith L, Reilly MM. Plasma neurofilament heavy chain is not a useful biomarker in Charcot-Marie-Tooth disease. Muscle Nerve. 2016 Jun;53(6):972-5. Epub 2016 Apr 27. PubMed PMID: 27015106.

138. Tomaselli, PJ, Rossor AM, Polke JM, Poh R, Blake J, & Reilly MM (2016). Semi dominant mutations in MFN2-related neuropathy and implications for genetic counselling. Journal of the peripheral nervous system: JPNS, 21(1), 52-54. PMID: 26968437

139. Lunn MP, Ellis L, Hadden RD, Rajabally YA, Winer JB, Reilly MM. A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies. J Peripher Nerv Syst. 2016 Jan 12. PMID: 26757367

Francesco Muntoni

140. *Løseth S, Voermans NC, Torbergsen T, Lillis S, Jonsrud C, Lindal S, Kamsteeg EJ, Lammens M, Broman M, Dekomien G, Maddison P, Muntoni F, Sewry C, Radunovic A, de Visser M, Straub V, van Engelen B, Jungbluth H. A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. J Neurol. 2013 Jun;260(6):1504-10. PMID: 23329375

13 | P a g e 141. Oates EC, Rossor AM, Hafezparast M, Gonzalez M, Speziani F, Macarthur DG, Lek M, Cottenie E, Scoto M, Foley AR, Hurles M, Houlden H, Greensmith L, Auer-Grumbach M, Pieber TR, Strom TM, Schule R, Herrmann DN, Sowden JE, Acsadi G, Menezes MP, Clarke NF, Züchner S; UK10K, Muntoni F, North KN, Reilly MM. Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia. American Journal of Human Genetics 92, 1–9, June 6, 2013. PMID: 23664120

142. Ricotti V, Ridout DA, Scott E, Quinlivan R, Robb SA, Manzur AY, Muntoni F; on behalf of the NorthStar Clinical Network. Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne Muscular Dystrophy. J Neurol Neurosurg Psychiatry. 2013 Jun;84:698-705. PMID: 23250964

143. Pane M, Scalise R, Berardinelli A, D'Angelo G, Ricotti V, Alfieri P, Moroni I, Hartley L, Pera MC, Baranello G, Catteruccia M, Casalino T, Romeo DM, Graziano A, Gandioli C, Bianco F, Mazzone ES, Lombardo ME, Scoto M, Sivo S, Palermo C, Gualandi F, Sormani MP, Ferlini A, Bertini E, Muntoni F, Mercuri E. Early neurodevelopmental assessment in Duchenne muscular dystrophy. Neuromuscul Disord. 2013 Jun;23:451-5. PMID: 23535446

144. Burns J, Menezes M, Finkel RS, Estilow T, Moroni I, Pagliano E, Laurá M, Muntoni F, Herrmann DN, Eichinger K, Shy R, Pareyson D, Reilly MM, Shy ME. Transitioning outcome measures: relationship between the CMTPedS and CMTNSv2 in children, adolescents, and young adults with Charcot-Marie-Tooth disease. J Peripher Nerv Syst. 2013 Jun;18:177-80. PMID: 23781965

145. *Garralda ME, McConachie H, Le Couteur A, Sriranjan S, Chakrabarti I, Cirak S, Guglieri M, Bushby K, Muntoni F. Emotional impact of genetic trials in progressive paediatric disorders: a dose-ranging exon-skipping trial in Duchenne muscular dystrophy. Child Care Health Dev. 2013 May;39(3):449-55. PMID: 22676208

146. Mitrpant C, Porensky P, Zhou H, Price L, Muntoni F, Fletcher S, Wilton SD, Burghes AH. Improved Antisense Oligonucleotide Design to Suppress Aberrant SMN2 Gene Transcript Processing: Towards a Treatment for Spinal Muscular Atrophy. PLoS One. 2013 Apr 22;8(4):e6211.4; PMID; 23630626

147. Maggi L, Scoto M, Cirak S, Robb SA, Klein A, Lillis S, Cullup T, Feng L, Manzur AY, Sewry CA, Abbs S, Jungbluth H, Muntoni F. Congenital myopathies - Clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom. Neuromuscul Disord. 2013 Mar;23:195-205. PMID: 233947884

148. Burke G, Hiscock A, Klein A, Niks EH, Main M, Manzur AY, Ng J, de Vile C, Muntoni F, Beeson D, Robb S. benefits children with congenital myasthenic syndrome due to DOK7 mutations. Neuromuscul Disord. 2013. Feb;23(2):170-5. PMID: 23219351

149. Stevens E, Crass K, Cirak S, Foley R, Torelli S, Willer T, Manzini C, Yau S, Brodd L, Sewry CA, Feng L, Haliloglu G, Orhan G, Walsh C, Hurles M, Campbell K,3 UK10K consortium, Stemple D, Lin Y, Muntoni F. Mutations in B3GALNT2 cause congenital muscular dystrophy with hypoglycosylation of alpha-dystroglycan. AJHG, 2013 Mar 7;92(3):354-65. PMID: 23453667

150. Zhou H, Janghra N, Mitrpant C, Dickinson RL, Anthony K, Price L, Eperon IC, Wilton S, Morgan J, Muntoni F. A Novel Morpholino Oligomer Targeting ISS-N1 Improves Rescue of Severe SMA Transgenic Mice. Human Gene Therapy, 2013 Mar;24:331-42. PMID: 23339722

151. Pitceathly RD, Taanman JW, Rahman S, Meunier B, Sadowski M, Cirak S, Hargreaves I, Land JM, Nanji T, Polke JM, Woodward CE, Sweeney MG, Solanki S, Foley AR, Hurles ME, Stalker J, Blake J, Holton JL, Phadke R, Muntoni F, Reilly MM, Hanna MG; for the

14 | P a g e UK10K Consortium. COX10 mutations resulting in complex multisystem mitochondrial disease that remains stable into adulthood. JAMA Neurol. 2013. Dec;70(12):1556-61. PMID: 24100867

152. Gupta VA, Ravenscroft G, Shaheen R, Todd EJ, Swanson LC, Shiina M, Ogata K, Hsu C, Clarke NF, Darras BT, Farrar MA, Hashem A, Manton ND, Muntoni F, North KN, Sandaradura SA, Nishino I, Hayashi YK, Sewry CA, Thompson EM, Yau KS, Brownstein CA, Yu TW, Allcock RJ, Davis MR, Wallgren-Pettersson C, Matsumoto N, Alkuraya FS, Laing NG, Beggs AH. Identification of KLHL41 Mutations Implicates BTB-Kelch-Mediated Ubiquitination as an Alternate Pathway to Myofibrillar Disruption in Nemaline Myopathy. Am J Hum Genet. 2013 Dec. 5;93(6):1108-17. PMID: 24268659

153. *Foley AR, Quijano-Roy S, Collins J, Straub V, McCallum M, Deconinck N, Mercuri E, Pane M, D'Amico A, Bertini E, North K, Ryan MM, Richard P, Allamand V, Hicks D, Lamandé S, Hu Y, Gualandi F, Auh S, Muntoni F, Bönnemann CG. Natural history of pulmonary function in collagen VI-related myopathies. Brain. 2013 Dec;136(Pt 12):3625-33. PMID: 24268659

154. *Zaharieva IT, Calissano M, Scoto M, Preston M, Cirak S, Feng L, Collins J, Kole R, Guglieri M, Straub V, Bushby K, Ferlini A, Morgan JE, Muntoni F. Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne Muscular dystrophy. PLoS One. 2013 No.;8(11):e80263. PMID: 24282529

155. Jaffer F, Reilly MM, Quinlivan R, Muntoni F, Turner C, Parton M, Lunn M, Hilton- Jones D, Korkodilos M, Hanna MG. Emergency Neuromuscular Admissions are avoidable: a regional audit of unplanned hospital admissions of neuromuscular patients 2009-2011: Final results and recommendations. J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):e2. WOS: 000329373100144.

156. Klein A, Pitt MC, McHugh JC, Niks EH, Sewry CA, Phadke R, Feng L, Manzur AY, Tirupathi S, Devile C, Jayawant S, Finlayson S, Palace J, Muntoni F, Beeson D, Robb SA.DOK7 congenital myasthenic syndrome in childhood: Early diagnostic clues in 23 children. Neuromuscul Disord. 2013 Nov; 23(11):883-891. PMID: 23831158.

157. *Mayhew AG, Cano SJ, Scott E, Eagle M, Bushby K, Manzur A, Muntoni F. Detecting meaningful change using the North Star Ambulatory Assessment in Duchenne muscular dystrophy. Dev Med Child Neurol. 2013 Nov;55(11):1046-1052. PMID: 23900763.

158. Rokach O, Ullrich ND, Rausch M, Mouly V, Zhou H, Muntoni F, Zorzato F, Treves S. Establishment of a human skeletal muscle-derived cell line: biochemical, cellular and electrophysiological characterization. Biochem J. 2013 Oct 15;455(2):169-77. PMID: 23905709.

159. Paco S, Kalko SG, Jou C, Rodriguez RA, Corbera J, Muntoni F, Feng L, Rivas E, Torner F, Gualandi F, Gomez-Foix AM, Ferrer A, Ortez C, Nascimento A, Colomrer J, Jimenez-Mallebrera C. Gene Expression Profiling Identifies Molecular Pathways Associated with Collagen VI Deficiency and Provides Novel Therapeutic Targets. PLoS One. 2013 Oct 11;8(10):e77430. PMID: 24223098.

160. Fletcher S, Meloni PL, Johnsen RD, Wong BL, Muntoni F, Wilton SD. Antisense suppression of donor splice site mutations in the dystrophin gene transcript. Mol Genet Genomic Med. 2013 Sep;1(3):162-73. PMID: 24498612.

161. *Mazzone E, Bianco F, Main M, van den Hauwe M, Ash M, de Vries R, Fagoaga Mata J, Stein S, De Sanctis R, D'Amico A, Palermo C, Fanelli L, Scoto MC, Mayhew A, Eagle M, Vigo M, Febrer A, Korinthenberg R, de Visser M, Bushby K, Muntoni F, Goemans N, Sormani MP, Bertini E, Pane M, Mercuri E. Six minute walk test in type III spinal muscular

15 | P a g e atrophy: A 12 month longitudinal study. Neuromuscul Disord. Neuromuscul Disord. 2013 Aug;23(8):624-8. d. PMID: 23809874.

162. *Sarkozy A, Hicks D, Hudson J, Laval SH, Barresi R, Hilton-Jones D, Deschauer M, Harris E, Rufibach L, Hwang E, Bashir R, Walter MC, Krause S, van den Bergh P, Illa I, Pénisson-Besnier I, De Waele L, Turnbull D, Guglieri M, Schrank B, Schoser B, Seeger J, Schreiber H, Gläser D, Eagle M, Bailey G, Walters R, Longman C, Norwood F, Winer J, Muntoni F, Hanna M, Roberts M, Bindoff LA, Brierley C, Cooper RG, Cottrell DA, Davies NP, Gibson A, Gorman GS, Hammans S, Jackson AP, Khan A, Lane R, McConville J, McEntagart M, Al-Memar A, Nixon J, Panicker J, Parton M, Petty R, Price CJ, Rakowicz W, Ray P, Schapira AH, Swingler R, Turner C, Wagner KR, Maddison P, Shaw PJ, Straub V, Bushby K, Lochmüller H. ANO5 Gene Analysis in a Large Cohort of Patients with Anoctaminopathy: Confirmation of Male Prevalence and High Occurrence of the Common Exon 5 Gene Mutation. Hum Mutat. 2013 Aug;34:1111-8. PMID: 23606453.

163. Zhou H, Rokach O, Feng L, Munteanu I, Mamchaoui K, Wilmshurst JM, Sewry C, Manzur AY, Pillay K, Mouly V, Duchen M, Jungbluth H, Treves S, Muntoni F. RyR1 Deficiency in Congenital Myopathies Disrupts Excitation-Contraction Coupling. Hum Mutat. 2013 Jul;34(7):986-96. PMID: 23553787.

164. Stevens E, Torelli S, Feng L, Phadke R, Walter MC, Schneiderat P, Eddaoudi A, Sewry CA, Muntoni F. Flow Cytometry for the Analysis of a-Dystroglycan Glycosylation in Fibroblasts from Patients with Dystroglycanopathies. PLoS One. 2013 Jul 22;8(7):e68958. PMD: 23894383.

165. Carss KJ, Stevens E, Foley AR, Cirak S, Riemersma M, Torelli S, Hoischen A, Willer T, van Scherpenzeel M, Moore SA, Messina S, Bertini E, Bönnemann CG, Abdenur JE, Grosmann CM, Kesari A, Punetha J, Quinlivan R, Waddell LB, Young HK, Wraige E, Yau S, Brodd L, Feng L, Sewry C, Macarthur DG, North KN, Hoffman E, Stemple DL, Hurles ME, van Bokhoven H, Campbell KP, Lefeber DJ; UK10K Consortium, Lin YY, Muntoni F. Mutations in GDP-Mannose Pyrophosphorylase B Cause Congenital and Limb-Girdle Muscular Dystrophies Associated with Hypoglycosylation of alpha-Dystroglycan. Am J Hum Genet. 2013 Jul; 93(1):29-41. PMID: 23768512.

166. Ravenscroft G, Miyatake S, Lehtokari VL, Todd EJ, Vornanen P, Yau KS, Hayashi YK, Miyake N, Tsurusaki Y, Doi H, Saitsu H, Osaka H, Yamashita S, Ohya T, Sakamoto Y, Koshimizu E, Imamura S, Yamashita M, Ogata K, Shiina M, Bryson-Richardson RJ, Vaz R, Ceyhan O, Brownstein CA, Swanson LC, Monnot S, Romero NB, Amthor H, Kresoje N, Sivadorai P, Kiraly-Borri C, Haliloglu G, Talim B, Orhan D, Kale G, Charles AK, Fabian VA, Davis MR, Lammens M, Sewry CA, Manzur A, Muntoni F, Clarke NF, North KN, Bertini E, Nevo Y, Willichowski E, Silberg IE, Topaloglu H, Beggs AH, Allcock RJ, Nishino I, Wallgren- Pettersson C, Matsumoto N, Laing NG. Mutations in KLHL40 Are a Frequent Cause of Severe Autosomal-Recessive Nemaline Myopathy. Am J Hum Genet. 2013 Jul 11;93(1):6- 18. PMID: 23746549.

167. *Quinlivan R, Mitsuahashi S, Sewry C, Cirak S, Aoyama C, Mooore D, Abbs S, Robb S, Newton T, Moss C, Birchall D, Sugimoto H, Bushby K, Guglieri M, Muntoni F, Nishino I, Straub V. Muscular dystrophy with large mitochondria associated with mutations in the CHKB gene in three British patients: Extending the clinical and pathological phenotype. Neuromuscul Disord. 2013 Jul;23:549-56. PMID: 23692895.

168. *Dlamini N, Voermans NC, Lillis S, Stewart K, Kamsteeg EJ, Drost G, Quinlivan R, Snoeck M, Norwood F, Radunovic A, Straub V, Roberts M, Vrancken AF, van der Pol WL, de Coo RI, Manzur AY, Yau S, Abbs S, King A, Lammens M, Hopkins PM, Mohammed S, Treves S, Muntoni F, Wraige E, Davis MR, van Engelen B, Jungbluth H. Mutations in RYR1

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178. Fernandez-Fuente M, Martin-Duque P, Vassaux G, Brown SC, Muntoni F, Terracciano CM, Piercy RJ. Adenovirus-mediated expression of myogenic differentiation factor 1 (MyoD) in equine and human dermal fibroblasts enables their conversion to caffeine-sensitive myotubes. Neuromuscul Disord. 2014 Mar;24(3):250-8. PMID: 24342283

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183. Foley AR, Pitceathly RD, He J, Kim J, Pearson NM, Muntoni F, Hanna MG. Whole- genome sequencing and the clinician: a tale of two cities. J Neurol Neurosurg Psychiatry. 2014: PMID: 24706943

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186. *Voit T, Topaloglu H, Straub V, Muntoni F, Deconinck N, Campion G, De Kimpe SJ, Eagle M, Guglieri M, Hood S, Liefaard L, Lourbakos A, Morgan A, Nakielny J,Quarcoo N, Ricotti V, Rolfe K, Servais L, Wardell C, Wilson R, Wright P, Kraus JE. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014 Oct;13(10):987-96 PMID: 25209738.

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189. Ricotti V, Mandy WP, Scoto M, Pane M, Deconinck N, Messina S, Mercuri E, Skuse DH, Muntoni F. Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations. Dev Med Child Neurol. 2016 Jan;58(1):77-84. doi: 10.1111/dmcn.12922. Epub 2015 Sep 14. PMID: 26365034

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192. Sanmaneechai O, Feely S, Scherer SS, Herrmann DN, Burns J, Muntoni F, Li J, Siskind CE, Day JW, Laura M, Sumner CJ, Lloyd TE, Ramchandren S, Shy RR, Grider T, Bacon C, Finkel RS, Yum SW, Moroni I, Piscosquito G, Pareyson D, Reilly MM, Shy ME; Inherited Neuropathies Consortium - Rare Disease Clinical Research Consortium (INC- RDCRC). Genotype-phenotype characteristics and baseline natural history of heritable neuropathies caused by mutations in the MPZ gene. Brain. 2015 Nov;138(Pt 11):3180-92. Epub 2015 Aug 25. PMID: 26310628

193. Zhou H, Meng J, Marrosu E, Janghra N, Morgan J, Muntoni F. Repeated low doses of morpholino antisense oligomer: an intermediate mouse model of spinal muscular atrophy to explore the window of therapeutic response. Hum Mol Genet. 2015 Nov 15;24(22):6265-77. Epub 2015 Aug 11. PMID: 26264577

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195. Mazzone E, Montes J, Main M, Mayhew A, Ramsey D, Glanzman AM, Dunaway S, Salazar R, Pasternak A, Quigley J, Pane M, Pera MC, Scoto M, Messina S, Sframeli M, D'amico A, Van Den Hauwe M, Sivo S, Goemans N, Darras BT, Kaufmann P, Bertini E, De Vivo DC, Muntoni F, Finkel R, Mercuri E. Old measures and new scores in spinal muscular atrophy patients. Muscle Nerve. 2015 Sep;52(3):435-7. doi: 10.1002/mus.24748. Epub 2015 Jul 24. PMID: 26111847

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197. Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzales MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Reply: The p.Ser107Leu in BICD2 is a mutation 'hot spot' causing distal spinal muscular atrophy. Brain. 2015 Nov;138(Pt 11):e392. Epub 2015 Jun 10. No abstract available. PMID: 26063657

198. Finkel R, Bertini E, Muntoni F, Mercuri E; ENMC SMA Workshop Study Group.209th ENMC International Workshop: Outcome Measures and Clinical Trial Readiness in Spinal Muscular Atrophy 7-9 November 2014, Heemskerk, The Netherlands. Neuromuscul Disord. 2015 Jul;25(7):593-602. Epub 2015 Apr 28. No abstract available. PMID: 26045156

199. Rokach O, Sekulic-Jablanovic M, Voermans N, Wilmshurst J, Pillay K, Heytens L, Zhou H, Muntoni F, Gautel M, Nevo Y, Mitrani-Rosenbaum S, Attali R, Finotti A, Gambari R, Mosca B, Jungbluth H, Zorzato F, Treves S. Epigenetic changes as a common trigger of muscle weakness in congenital myopathies. Hum Mol Genet. 2015 Aug 15;24(16):4636-47. Epub 2015 May 27. PMID: 26019235

200. Paco S, Kalko SG, Jou C, Rodríguez MA, Corbera J, Muntoni F, Feng L, Rivas E, Torner F, Gualandi F, Gomez-Foix AM, Ferrer A, Ortez C, Nascimento A, Colomer J, Jimenez-Mallebrera C. Correction: Gene Expression Profiling Identifies Molecular Pathways Associated with Collagen VI Deficiency and Provides Novel Therapeutic Targets. PLoS One. 2015 May 14;10(5):e0128614. doi: 10.1371/journal.pone.0128614. eCollection 2015. No abstract available. PMID: 25974264

201. Byrne S, Dlamini N, Lumsden D, Pitt M, Zaharieva I, Muntoni F, King A, Robert L, Jungbluth H. SIL1-related Marinesco-Sjoegren syndrome (MSS) with associated motor neuronopathy and bradykinetic movement disorder. Neuromuscul Disord. 2015 Jul;25(7):585-8. PMID: 25958341

203. Meng J, Bencze M, Asfahani R, Muntoni F, Morgan JE. The effect of the muscle environment on the regenerative capacity of human skeletal muscle stem cells. Skelet Muscle. 2015 Apr 28;5:11. eCollection 2015. PMID: 25949786

204. Mercuri E, Muntoni F. Efficacy of idebenone in Duchenne muscular dystrophy. Lancet. 2015 May 2;385(9979):1704-6. Epub 2015 Apr 20. PMID: 25907159

205. Astrea G, Munteanu I, Cassandrini D, Lillis S, Trovato R, Pegoraro E, Cioni G, Mercuri E, Muntoni F, Battini R. A diagnostic dilemma in a family with cystinuria type B resolved by muscle magnetic resonance. Pediatr Neurol. 2015 May;52(5):548-51. Epub 2015 Feb 7. PMID: 25882082

206. Brunklaus A, Parish E, Muntoni F, Scuplak S, Tucker SK, Fenton M, Hughes ML, Manzur AY. The value of cardiac MRI versus echocardiography in the pre-operative assessment of patients with Duchenne muscular dystrophy. Eur J Paediatr Neurol. 2015 Jul;19(4):395-401. doi: 10.1016/j.ejpn.2015.03.008. Epub 2015 Mar 24. PMID: 25843299

207. Meilleur KG, Jain MS, Hynan LS, Shieh CY, Kim E, Waite M, McGuire M, Fiorini C, Glanzman AM, Main M, Rose K, Duong T, Bendixen R, Linton MM, Arveson IC, Nichols C,

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208. *Lynn S, Aartsma-Rus A, Bushby K, Furlong P, Goemans N, De Luca A, Mayhew A, McDonald C, Mercuri E, Muntoni F, Pohlschmidt M, Verschuuren J, Voit T, Vroom E, Wells DJ, Straub V. Measuring clinical effectiveness of medicinal products for the treatment of Duchenne muscular dystrophy. Neuromuscul Disord. 2015 Jan;25(1):96-105. PMID: 25307856.

209. Colombo I, Scoto M, Manzur AY, Robb SA, Maggi L, Gowda V, Cullup T, Yau M, Phadke R, Sewry C, Jungbluth H, Muntoni F. Congenital myopathies: Natural history of a large pediatric cohort. Neurology. 2015 Jan 6;84(1):28-35. PMID: 25428687

210. Fridman V, Bundy B, Reilly MM, Pareyson D, Bacon C, Burns J, Day J, Feely S, Finkel RS, Grider T, Kirk CA, Herrmann DN, Laurá M, Li J, Lloyd T, Sumner CJ, Muntoni F, Piscosquito G, Ramchandren S, Shy R, Siskind CE, Yum SW, Moroni I, Pagliano E, Zuchner S, Scherer SS, Shy ME; Inherited Neuropathies Consortium. CMT subtypes and disease burden in patients enrolled in the Inherited Neuropathies Consortium natural history study: a cross-sectional analysis. J Neurol Neurosurg Psychiatry. 2015 Aug;86(8):873-8. PMID: 25430934.

211. De Sanctis R, Pane M, Sivo S, Ricotti V, Baranello G, Frosini S, Mazzone E, Bianco F, Fanelli L, Main M, Corlatti A, D'Amico A, Colia G, Scalise R, Palermo C, Alfonsi C, Tritto G, Romeo DM, Graziano A, Battini R, Morandi L, Bertini E, Muntoni F, Mercuri E. Suitability of North Star Ambulatory Assessment in young boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2015 Jan;25(1):14-8. PMID: 25454732.

212. Muntoni F, Cross JH. Paediatric neurology: from molecular mechanisms to targeted treatments. Lancet Neurol. 2015 Jan;14(1):16-8 PMID: 25496887.

213. Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzalez MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain. 2015 Feb;138(Pt 2):293-310 PMID: 25497877

214. *Ferlini A, Flanigan KM, Lochmuller H, Muntoni F, 't Hoen PA, McNally E. 204th ENMC International Workshop on Biomarkers in Duchenne Muscular Dystrophy 24-26 January 2014, Naarden, The Netherlands. Neuromuscul Disord. 2015 Feb;25(2):184-98. PMID: 25529833.

215. Scoto M, Rossor AM, Harms MB, Cirak S, Calissano M, Robb S, Manzur AY, Martínez Arroyo A, Rodriguez Sanz A, Mansour S, Fallon P, Hadjikoumi I, Klein A, Yang M, De Visser M, Overweg-Plandsoen WC, Baas F, Taylor JP, Benatar M, Connolly AM, Al-Lozi MT, Nixon J, de Goede CG, Foley AR, Mcwilliam C, Pitt M, Sewry C, Phadke R, Hafezparast M, Chong WK, Mercuri E, Baloh RH, Reilly MM, Muntoni F. Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy. Neurology. 2015 Feb 17;84(7):668-79. PMID: 25609763

216. Graziano A, Bianco F, D'Amico A, Moroni I, Messina S, Bruno C, Pegoraro E, Mora M, Astrea G, Magri F, Comi GP, Berardinelli A, Moggio M, Morandi L, Pini A, Petillo R, Tasca G, Monforte M, Minetti C, Mongini T, Ricci E, Gorni K, Battini R, Villanova M, Politano L, Gualandi F, Ferlini A, Muntoni F, Santorelli FM, Bertini E, Pane M, Mercuri E. Prevalence of

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217. Ricotti V, Ridout DA, Pane M, Main M, Mayhew A, Mercuri E, Manzur AY, Muntoni F; on behalf of UK NorthStar Clinical Network. The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy: considerations for the design of clinical trials. J Neurol Neurosurg Psychiatry. 2015 Mar 2. PMID: 25733532.

218. Sewry CA, Holton JL, Dick DJ, Muntoni F, Hanna MG. Zebra body myopathy is caused by a mutation in the skeletal muscle actin gene (ACTA1). Neuromuscul Disord. 2015 May;25(5):388-91. PMID: 25747004.

219. Brunklaus A, Parish E, Muntoni F, Scuplak S, Tucker SK, Fenton M, Hughes ML, Manzur AY. The value of cardiac MRI versus echocardiography in the pre-operative assessment of patients with Duchenne muscular dystrophy. Eur J Paediatr Neurol. 2015 Jul;19(4):395-401. PMID: 25843299.

220. Astrea G, Munteanu I, Cassandrini D, Lillis S, Trovato R, Pegoraro E, Cioni G, Mercuri E, Muntoni F, Battini R. A diagnostic dilemma in a family with cystinuria type B resolved by muscle magnetic resonance. Pediatr Neurol. 2015 May;52(5):548-51. PMID: 25882082.

221. Mercuri E, Muntoni F. Efficacy of idebenone in Duchenne muscular dystrophy. Lancet. 2015 May 2;385(9979):1704-6. PMID: 25907159.

222. Byrne S, Dlamini N, Lumsden D, Pitt M, Zaharieva I, Muntoni F, King A, Robert L, Jungbluth H. SIL1-related Marinesco-Sjoegren syndrome (MSS) with associated motor neuronopathy and bradykinetic movement disorder. Neuromuscul Disord. 2015 Jul;25(7):585-8. PMID: 25958341.

223. Rokach O, Sekulic-Jablanovic M, Voermans N, Wilmshurst J, Pillay K, Heytens L, Zhou H, Muntoni F, Gautel M, Nevo Y, Mitrani-Rosenbaum S, Attali R, Finotti A, Gambari R, Mosca B, Jungbluth H, Zorzato F, Treves S. Epigenetic changes as a common trigger of muscle weakness in congenital myopathies. Hum Mol Genet. 2015 Aug 15;24(16):4636-47. PMID: 26019235.

224. Finkel R, Bertini E, Muntoni F, Mercuri E; ENMC SMA Workshop Study Group. 209th ENMC International Workshop: Outcome Measures and Clinical Trial Readiness in Spinal Muscular Atrophy 7-9 November 2014, Heemskerk, The Netherlands. Neuromuscul Disord. 2015 Jul;25(7):593-602. PMID: 26045156.

225. Mercuri E, Finkel R, Montes J, Mazzone ES, Sormani MP, Main M, Ramsey D, Mayhew A, Glanzman AM, Dunaway S, Salazar R, Pasternak A, Quigley J, Pane M, Pera MC, Scoto M, Messina S, Sframeli M, Vita GL, D'Amico A, van den Hauwe M, Sivo S, Goemans N, Kaufmann P, Darras BT, Bertini E, Muntoni F, De Vivo DC. Patterns of disease progression in type 2 and 3 SMA: Implications for clinical trials. Neuromuscul Disord. 2016 Feb;26(2):126-31. doi: 10.1016/j.nmd.2015.10.006. Epub 2015 Dec 3. PMID: 26776503

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228. Ricotti V, Muntoni F, Voit T. Challenges of clinical trial design for DMD. Neuromuscul Disord. 2015 Dec;25(12):932-5. Epub 2015 Oct 23. PMID: 26584589

229. Ricotti V, Jägle H, Theodorou M, Moore AT, Muntoni F, Thompson DA. Ocular and neurodevelopmental features of Duchenne muscular dystrophy: a signature of dystrophin function in the central nervous system. Eur J Hum Genet. 2015 Jun 17. PMID: 26081639

230. Mazzone E, Montes J, Main M, Mayhew A, Ramsey D, Glanzman AM, Dunaway S, Salazar R, Pasternak A, Quigley J, Pane M, Pera MC, Scoto M, Messina S, Sframeli M, D'amico A, Van Den Hauwe M, Sivo S, Goemans N, Darras BT, Kaufmann P, Bertini E, De Vivo DC, Muntoni F, Finkel R, Mercuri E. Old measures and new scores in spinal muscular atrophy patients. Muscle Nerve. 2015 Jun 25. PMID: 26111847.

231. *Belaya K, Rodríguez Cruz PM, Liu WW, Maxwell S, McGowan S, Farrugia ME, Petty R, Walls TJ, Sedghi M, Basiri K, Yue WW, Sarkozy A, Bertoli M, Pitt M, Kennett R, Schaefer A, Bushby K, Parton M, Lochmüller H, Palace J, Muntoni F, Beeson D. Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies. Brain. 2015 Jun 30. pii: awv185. [Epub ahead of print PMID: 26133662.

232. De Goede C, Oh T, Joseph J, Muntoni F, Sewry C, Phadke R. Choline Kinase Beta- Related Muscular Dystrophy, Appearance of Muscle Involvement on Magnetic Resonance Imaging. Pediatr Neurol. 2016 Jan;54:49-54. doi: 10.1016/j.pediatrneurol.2015.09.018. Epub 2015 Nov 6. PMID: 26548592

233. Somers E, Lees RD, Hoban K, Sleigh JN, Zhou H, Muntoni F, Talbot K, Gillingwater TH, Parson SH. Vascular Defects and Spinal Cord Hypoxia in Spinal Muscular Atrophy. Ann Neurol. 2016 Feb;79(2):217-30. doi: 10.1002/ana.24549. Epub 2016 Jan 13. PMID: 26506088

234. Lopez RJ, Byrne S, Vukcevic M, Sekulic-Jablanovic M, Xu L, Brink M, Alamelu J, Voermans N, Snoeck M, Clement E, Muntoni F, Zhou H, Radunovic A, Mohammed S, Wraige E, Zorzato F, Treves S, Jungbluth H. An RYR1 mutation associated with malignant hyperthermia is also associated with bleeding abnormalities.Sci Signal. 2016 Jul 5;9(435):ra68. PMID: 27382027

235. Jungbluth H, Dowling JJ, Ferreiro A, Muntoni F; RYR1 Myopathy Consortium. 217th ENMC International Workshop: RYR1-related myopathies, Naarden, The Netherlands, 29-31 January 2016. Neuromuscul Disord. 2016 Jun 7. pii: S0960-8966(16)30250-4. [Epub ahead of print] No abstract available. PMID: 27377473

236. Catapano F, Zaharieva I, Scoto M, Marrosu E, Morgan J, Muntoni F, Zhou H Altered Levels of MicroRNA-9, -206, and -132 in Spinal Muscular Atrophy and Their Response to Antisense Oligonucleotide Therapy.. Mol Ther Nucleic Acids. 2016 Jul 5;5(7):e331. PMID: 27377135

237. *Straub V, Balabanov P, Bushby K, Ensini M, Goemans N, De Luca A, Pereda A, Hemmings R, Campion G, Kaye E, Arechavala-Gomeza V, Goyenvalle A, Niks E,

23 | P a g e Veldhuizen O, Furlong P, Stoyanova-Beninska V, Wood MJ, Johnson A, Mercuri E, Muntoni F, Sepodes B, Haas M, Vroom E, Aartsma-Rus A.Stakeholder cooperation to overcome challenges in orphan medicine development: the example of Duchenne muscular dystrophy. Lancet Neurol. 2016 Jul;15(8):882-90. Review. PMID: 27302365

238. Alshaikh N, Brunklaus A, Davis T, Robb SA, Quinlivan R, Munot P, Sarkozy A, Muntoni F, Manzur AY; Dubowitz Neuromuscular Team. Vitamin D in corticosteroid-naïve and corticosteroid-treated Duchenne muscular dystrophy: what dose achieves optimal 25(OH) vitamin D levels? Arch Dis Child. 2016 May 31. [Epub ahead of print]. PMID: 27246070

239. Boldt K, van Reeuwijk J, Lu Q, Koutroumpas K, Nguyen TM, Texier Y, van Beersum SE, Horn N, Willer JR, Mans DA, Dougherty G, Lamers IJ, Coene KL, Arts HH, Betts MJ, Beyer T, Bolat E, Gloeckner CJ, Haidari K, Hetterschijt L, Iaconis D, Jenkins D, Klose F, Knapp B, Latour B, Letteboer SJ, Marcelis CL, Mitic D, Morleo M, Oud MM, Riemersma M, Rix S, Terhal PA, Toedt G, van Dam TJ, de Vrieze E, Wissinger Y, Wu KM, Apic G, Beales PL, Blacque OE, Gibson TJ, Huynen MA, Katsanis N, Kremer H, Omran H, van Wijk E, Wolfrum U, Kepes F, Davis EE, Franco B, Giles RH, Ueffing M, Russell RB, Roepman R; UK10K Rare Diseases Group. An organelle-specific protein landscape identifies novel diseases and molecular mechanisms. Nat Commun. 2016 May 13;7:11491. doi: 10.1038/ncomms11491. PMID: 27173435

240. Sintusek P, Catapano F, Angkathunkayul N, Marrosu E, Parson SH, Morgan JE, Muntoni F, Zhou H. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment. LoS One. 2016 May 10;11(5):e0155032. eCollection 2016. PMID: 27163330 [PubMed - in process]

241. O'Grady GL, Lek M, Lamande SR, Waddell L, Oates EC, Punetha J, Ghaoui R, Sandaradura SA, Best H, Kaur S, Davis M, Laing NG, Muntoni F, Hoffman E, MacArthur DG, Clarke NF, Cooper S, North K.Diagnosis and etiology of congenital muscular dystrophy: We are halfway there. Ann Neurol. 2016 Jul;80(1):101-11. doi: 10.1002/ana.24687. Epub 2016 May 25. PMID: 27159402

242. *Rodríguez Cruz PM, Belaya K, Basiri K, Sedghi M, Farrugia ME, Holton JL, Liu WW, Maxwell S, Petty R, Walls TJ, Kennett R, Pitt M, Sarkozy A, Parton M, Lochmüller H, Muntoni F, Palace J, Beeson D.Clinical features of the myasthenic syndrome arising from mutations in GMPPB. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):802-9. doi: 10.1136/jnnp-2016-313163. Epub 2016 May 4. PMID: 27147698 [PubMed - in process]

243. Heywood WE, Bliss E, Mills P, Yuzugulen J, Carreno G, Clayton PT, Muntoni F, Worthington VC, Torelli S, Sebire NJ, Mills K, Grunewald S. Global serum glycoform profiling for the investigation of dystroglycanopathies & Congenital Disorders of Glycosylation. Mol Genet Metab Rep. 2016 Apr 17;7:55-62. eCollection 2016 Jun. PMID: 27134828

244. Bergsma A, Lobo-Prat J, Vroom E, Furlong P, Herder JL; Workshop Participants. 1st Workshop on Upper-Extremity Assistive Technology for People with Duchenne: State of the art, emerging avenues, and challenges: April 27th 2015, London, United Kingdom. Neuromuscul Disord. 2016 Jun;26(6):386-93. doi: 10.1016/j.nmd.2016.04.005. Epub 2016 Apr 8. No abstract available. PMID: 27133663

245. Ricotti V, Spinty S, Roper H, Hughes I, Tejura B, Robinson N, Layton G, Davies K, Muntoni F, Tinsley J. Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2- Arylbenzoxazole Utrophin Modulator, following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy. PLoS One. 2016 Apr 7;11(4):e0152840. doi: 10.1371/journal.pone.0152840. eCollection 2016. PMID: 27055247

24 | P a g e [PubMed - in process]

246. Cornett KM, Menezes MP, Bray P, Halaki M, Shy RR, Yum SW, Estilow T, Moroni I, Foscan M, Pagliano E, Pareyson D, Laurá M, Bhandari T, Muntoni F, Reilly MM, Finkel RS, Sowden J, Eichinger KJ, Herrmann DN, Shy ME, Burns J; Inherited Neuropathies Consortium. Phenotypic Variability of Childhood Charcot-Marie-Tooth Disease. JAMA Neurol. 2016 Jun 1;73(6):645-51. doi: 10.1001/jamaneurol.2016.0171. PMID: 27043305 [PubMed - in process]

247. Janghra N, Morgan JE, Sewry CA, Wilson FX, Davies KE, Muntoni F, Tinsley J.Correlation of Utrophin Levels with the Dystrophin Protein Complex and Muscle Fibre Regeneration in Duchenne and Becker Muscular Dystrophy Muscle Biopsies. PLoS One. 2016 Mar 14;11(3):e0150818. doi: 10.1371/journal.pone.0150818. eCollection 2016. PMID: 26974331

248. *Scotton C, Bovolenta M, Schwartz E, Falzarano MS, Martoni E, Passarelli C, Armaroli A, Osman H, Rodolico C, Messina S, Pegoraro E, D'Amico A, Bertini E, Gualandi F, Neri M, Selvatici R, Boffi P, Maioli MA, Lochmüller H, Straub V, Bushby K, Castrignanò T, Pesole G, Sabatelli P, Merlini L, Braghetta P, Bonaldo P, Bernardi P, Foley R, Cirak S, Zaharieva I, Muntoni F, Capitanio D, Gelfi C, Kotelnikova E, Yuryev A, Lebowitz M, Zhang X, Hodge BA, Esser KA, Ferlini A. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy. J Cell Sci. 2016 Apr 15;129(8):1671- 84. doi: 10.1242/jcs.175927. Epub 2016 Mar 4. PMID: 26945058

249. Schoenmakers E, Carlson B, Agostini M, Moran C, Rajanayagam O, Bochukova E, Tobe R, Peat R, Gevers E, Muntoni F, Guicheney P, Schoenmakers N, Farooqi S, Lyons G, Hatfield D, Chatterjee K. Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis. J Clin Invest. 2016 Mar 1;126(3):992-6. Epub 2016 Feb 8. PMID: 26854926

250. *Meng J, Counsell JR, Reza M, Laval SH, Danos O, Thrasher A, Lochmüller H, Muntoni F, Morgan JE. Autologous skeletal muscle derived cells expressing a novel functional dystrophin provide a potential therapy for Duchenne Muscular Dystrophy. Sci Rep. 2016 Jan 27;6:19750. doi: 10.1038/srep19750. PMID: 26813695

Kate Bushby

251. Mayhew AG, Cano SJ, Scott E, Eagle M, Bushby K, Manzur A, Muntoni F; North Star Clinical Network for Neuromuscular Disease. Detecting meaningful change using the North Star Ambulatory Assessment in Duchenne muscular dystrophy. Dev Med Child Neurol. 2013 Nov;55(11):1046-52. Epub 2013 Aug 5. PMID: 23909763

252. Bladen CL, Rafferty K, Straub V, Monges S, Moresco A, Dawkins H, Roy A, Chamova T, Guergueltcheva V, Korngut L, Campbell C, Dai Y, Barišić N, Kos T, Brabec P, Rahbek J, Lahdetie J, Tuffery-Giraud S, Claustres M, Leturcq F, Ben Yaou R, Walter MC, Schreiber O, Karcagi V, Herczegfalvi A, Viswanathan V, Bayat F, de la Caridad Guerrero Sarmiento I, Ambrosini A, Ceradini F, Kimura E, van den Bergen JC, Rodrigues M, Roxburgh R, Lusakowska A, Oliveira J, Santos R, Neagu E, Butoianu N, Artemieva S, Rasic VM, Posada M, Palau F, Lindvall B, Bloetzer C, Karaduman A, Topaloğlu H, Inal S, Oflazer P, Stringer A, Shatillo AV, Martin AS, Peay H, Flanigan KM, Salgado D, von Rekowski B, Lynn S, Heslop E, Gainotti S, Taruscio D, Kirschner J, Verschuuren J, Bushby K, Béroud C, Lochmüller H. The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia. Hum Mutat. 2013 Nov;34(11):1449-57. Epub 2013 Aug 26. PMID: 23913485

25 | P a g e 253. Rodger S, Lochmüller H, Tassoni A, Gramsch K, König K, Bushby K, Straub V, Korinthenberg R, Kirschner J. The TREAT-NMD care and trial site registry: an online registry to facilitate clinical research for neuromuscular diseases. Orphanet J Rare Dis. 2013 Oct 23;8:171. PMID: 24148153

254. Hollingsworth KG, Garrood P, Eagle M, Bushby K, Straub V. Magnetic resonance imaging in Duchenne muscular dystrophy: longitudinal assessment of natural history over 18 months. Muscle Nerve. 2013 Oct;48(4):586-8. Epub 2013 Aug 30. PMID: 23620230

255. Hollingsworth KG, Willis TA, Bates MG, Dixon BJ, Lochmüller H, Bushby K, Bourke J, MacGowan GA, Straub V. Subepicardial dysfunction leads to global left ventricular systolic impairment in patients with limb girdle muscular dystrophy 2I. Eur J Heart Fail. 2013 Sep;15(9):986-94. Epub 2013 Apr 10. PMID: 23576288

256. Sarkozy A, Hicks D, Hudson J, Laval SH, Barresi R, Hilton-Jones D, Deschauer M, Harris E, Rufibach L, Hwang E, Bashir R, Walter MC, Krause S, van den Bergh P, Illa I, Pénisson-Besnier I, De Waele L, Turnbull D, Guglieri M, Schrank B, Schoser B, Seeger J, Schreiber H, Gläser D, Eagle M, Bailey G, Walters R, Longman C, Norwood F, Winer J, Muntoni F, Hanna M, Roberts M, Bindoff LA, Brierley C, Cooper RG, Cottrell DA, Davies NP, Gibson A, Gorman GS, Hammans S, Jackson AP, Khan A, Lane R, McConville J, McEntagart M, Al-Memar A, Nixon J, Panicker J, Parton M, Petty R, Price CJ, Rakowicz W, Ray P, Schapira AH, Swingler R, Turner C, Wagner KR, Maddison P, Shaw PJ, Straub V, Bushby K, Lochmüller H. ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation. Hum Mutat. 2013 Aug;34(8):1111-8. Epub 2013 Jun 12. PMID:23606453

257. Mazzone E, Bianco F, Main M, van den Hauwe M, Ash M, de Vries R, Fagoaga Mata J, Stein S, De Sanctis R, D'Amico A, Palermo C, Fanelli L, Scoto MC, Mayhew A, Eagle M, Vigo M, Febrer A, Korinthenberg R, de Visser M, Bushby K, Muntoni F, Goemans N, Sormani MP, Bertini E, Pane M, Mercuri E. Six minute walk test in type III spinal muscular atrophy: a 12 month longitudinal study. Neuromuscul Disord. 2013 Aug;23(8):624-8. Epub 2013 Jul 1. PMID: 23809874

258. Griggs RC, Herr BE, Reha A, Elfring G, Atkinson L, Cwik V, McColl E, Tawil R, Pandya S, McDermott MP, Bushby K. Corticosteroids in Duchenne muscular dystrophy: major variations in practice. Muscle Nerve. 2013 Jul;48(1):27-31. Epub 2013 Apr 25. PMID: 23483575

259. Connolly AM, Florence JM, Cradock MM, Malkus EC, Schierbecker JR, Siener CA, Wulf CO, Anand P, Golumbek PT, Zaidman CM, Philip Miller J, Lowes LP, Alfano LN, Viollet-Callendret L, Flanigan KM, Mendell JR, McDonald CM, Goude E, Johnson L, Nicorici A, Karachunski PI, Day JW, Dalton JC, Farber JM, Buser KK, Darras BT, Kang PB, Riley SO, Shriber E, Parad R, Bushby K, Eagle M; MDA DMD Clinical Research Network. Motor and cognitive assessment of infants and young boys with Duchenne Muscular Dystrophy: results from the Muscular Dystrophy Association DMD Clinical Research Network. Neuromuscul Disord. 2013 Jul;23(7):529-39. Epub 2013 May 28. PMID: 23726376

260. Quinlivan R, Mitsuahashi S, Sewry C, Cirak S, Aoyama C, Mooore D, Abbs S, Robb S, Newton T, Moss C, Birchall D, Sugimoto H, Bushby K, Guglieri M, Muntoni F, Nishino I, Straub V. Muscular dystrophy with large mitochondria associated with mutations in the CHKB gene in three British patients: extending the clinical and pathological phenotype. Neuromuscul Disord. 2013 Jul;23(7):549-56. Epub 2013 May 18. PMID: 23692895

26 | P a g e 261. Henderson M, De Waele L, Hudson J, Eagle M, Sewry C, Marsh J, Charlton R, He L, Blakely EL, Horrocks I, Stewart W, Taylor RW, Longman C, Bushby K, Barresi R. Recessive desmin-null muscular dystrophy with central nuclei and mitochondrial abnormalities. Acta Neuropathol. 2013 Jun;125(6):917-9. Epub 2013 Apr 11. PMID: 23575897

262. Harris E, Laval S, Hudson J, Barresi R, De Waele L, Straub V, Lochmüller H, Bushby K, Sarkozy A. Undiagnosed genetic muscle disease in the north of England: an in depth phenotype analysis. PLoS Curr. 2013 May 21;5. PMID: 23788081

263. Garralda ME, McConachie H, Le Couteur A, Sriranjan S, Chakrabarti I, Cirak S, Guglieri M, Bushby K, Muntoni F. Emotional impact of genetic trials in progressive paediatric disorders: a dose-ranging exon-skipping trial in Duchenne muscular dystrophy. Child Care Health Dev. 2013 May;39(3):449-55. Epub 2012 Jun 8. PMID: 22676208

264. Hornsey MA, Laval SH, Barresi R, Lochmüller H, Bushby K. Muscular dystrophy in dysferlin-deficient mouse models. Neuromuscul Disord. 2013 May;23(5):377-87. Epub 2013 Mar 7. Review. PMID: 23473732

265. McCormack P, Woods S, Aartsma-Rus A, Hagger L, Herczegfalvi A, Heslop E, Irwin J, Kirschner J, Moeschen P, Muntoni F, Ouillade MC, Rahbek J, Rehmann-Sutter C, Rouault F, Sejersen T, Vroom E, Straub V, Bushby K, Ferlini A. Guidance in social and ethical issues related to clinical, diagnostic care and novel therapies for hereditary neuromuscular rare diseases: "translating" the translational. PLoS Curr. 2013 Jan 10;5. PMID: 23330068

266. Wagner M, Chaouch A, Müller JS, Polvikoski T, Willis TA, Sarkozy A, Eagle M, Bushby K, Straub V, Lochmüller H. Presymptomatic late-onset Pompe disease identified by the dried blood spot test. Neuromuscul Disord. 2013 Jan;23(1):89-92. Epub 2012 Oct 10. PMID:23062590

267. Zaharieva IT, Calissano M, Scoto M, Preston M, Cirak S, Feng L, Collins J, Kole R, Guglieri M, Straub V, Bushby K, Ferlini A, Morgan JE, Muntoni F. Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne muscular Dystrophy. PLoS One. 2013 Nov 25;8(11):e80263.. eCollection 2013. PMID: 24282529

268. Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmüller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PLoS One. 2013 Aug 14;8(8):e70993. eCollection 2013. PMID: 23967145

269. Taruscio D, Gentile AE, De Santis M, Ferrelli RM, Posada de la Paz M, Hens M, Huizer J, Fregonese L, Stefanov R, Bottarelli V, Weinman A, Le Cam Y, Gavhed D, Mincarone P, Bushby K, Frazzica RG, Donati C, Vittozzi L, Jessop E. EUROPLAN: a project to support the development of national plans on rare diseases in Europe. Public Health Genomics. 2013;16(6):278-87. Epub 2014 Feb 3. PMID: 24503588

270. Pfeffer G, Barresi R, Wilson IJ, Hardy SA, Griffin H, Hudson J, Elliott HR, Ramesh AV, Radunovic A, Winer JB, Vaidya S, Raman A, Busby M, Farrugia ME, Ming A, Everett C, Emsley HC, Horvath R, Straub V, Bushby K, Lochmüller H, Chinnery PF, Sarkozy A. Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure. J Neurol Neurosurg Psychiatry. 2014 Mar;85(3):331-8. Epub 2013 Mar 13. PMID:23486992

27 | P a g e 271. Bladen CL, Thompson R, Jackson JM, Garland C, Wegel C, Ambrosini A, Pisano P, Walter MC, Schreiber O, Lusakowska A, Jedrzejowska M, Kostera-Pruszczyk A, van der Pol L, Wadman RI, Gredal O, Karaduman A, Topaloglu H, Yilmaz O, Matyushenko V, Rasic VM, Kosac A, Karcagi V, Garami M, Herczegfalvi A, Monges S, Moresco A, Chertkoff L, Chamova T, Guergueltcheva V, Butoianu N, Craiu D, Korngut L, Campbell C, Haberlova J, Strenkova J, Alejandro M, Jimenez A, Ortiz GG, Enriquez GV, Rodrigues M, Roxburgh R, Dawkins H, Youngs L, Lahdetie J, Angelkova N, Saugier-Veber P, Cuisset JM, Bloetzer C, Jeannet PY, Klein A, Nascimento A, Tizzano E, Salgado D, Mercuri E, Sejersen T, Kirschner J, Rafferty K, Straub V, Bushby K, Verschuuren J, Beroud C, Lochmüller H. Mapping the differences in care for 5,000 spinal muscular atrophy patients, a survey of 24 national registries in North America, Australasia and Europe. J Neurol. 2014 Jan;261(1):152-63. Epub 2013 Oct 27. PMID: 24162038

272. Graham CD, Weinman J, Sadjadi R, Chalder T, Petty R, Hanna MG, Turner C, Parton M, Maddison P, Radunovic A, Longman C, Robb Y, Bushby K, Hilton-Jones D, Rose MR. A multicentre postal survey investigating the contribution of illness perceptions, coping and optimism to quality of life and mood in adults with muscle disease. Clin Rehabil. 2014 May;28(5):508-19. Epub 2013 Nov 15. PMID: 24240060

273. Hicks D, Farsani GT, Laval S, Collins J, Sarkozy A, Martoni E, Shah A, Zou Y, Koch M, Bönnemann CG, Roberts M, Lochmüller H, Bushby K, Straub V. Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy. Hum Mol Genet. 2014 May 1;23(9):2353-63. Epub 2013 Dec13. PMID: 24334769

274. Lochmüller H, Bushby K. Becker and Duchenne muscular dystrophy: a two-way information process for therapies. J Neurol Neurosurg Psychiatry. 2014 Jan;85(1):5-6. Epub 2013 May 21. PMID:23695496

275. Chaouch A, Porcelli V, Cox D, Edvardson S, Scarcia P, De Grassi A, Pierri CL, Cossins J, Laval SH, Griffin H, Müller JS, Evangelista T, Töpf A, Abicht A, Huebner A, von der Hagen M, Bushby K, Straub V, Horvath R, Elpeleg O, Palace J, Senderek J, Beeson D, Palmieri L, Lochmüller H. Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. J Neuromuscul Dis. 2014;1(1):75-90. PMID: 26870663

276. Anthony K, Arechavala-Gomeza V, Ricotti V, Torelli S, Feng L, Janghra N, Tasca G, Guglieri M, Barresi R, Armaroli A, Ferlini A, Bushby K, Straub V, Ricci E, Sewry C, Morgan J, Muntoni F. Biochemical characterization of patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 skipping. JAMA Neurol. 2014 Jan;71(1):32-40. PMID: 24217213

277. Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmuller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross-sectional study. PLoS One. 2014 Feb 28;9(2):e90377. eCollection 2014. PMID: 24587344

278. Bushby KM, Collins J, Hicks D. Collagen type VI myopathies. Adv Exp Med Biol. 2014;802:185-99. Review. PMID:24443028

279. Taruscio D, Gentile AE, Evangelista T, Frazzica RG, Bushby K, Montserrat AM. Centres of Expertise and European Reference Networks: key issues in the field of

28 | P a g e rare diseases. The EUCERD Recommendations. Blood Transfus. 2014 Apr;12 Suppl 3:s621-5. PMID: 24922304

280. Mazzone E, De Sanctis R, Fanelli L, Bianco F, Main M, van den Hauwe M, Ash M, de Vries R, Fagoaga Mata J, Schaefer K, D'Amico A, Colia G, Palermo C, Scoto M, Mayhew A, Eagle M, Servais L, Vigo M, Febrer A, Korinthenberg R, Jeukens M, de Viesser M, Totoescu A, Voit T, Bushby K, Muntoni F, Goemans N, Bertini E, Pane M, Mercuri E. Hammersmith Functional Motor Scale and Motor Function Measure-20 in non ambulant SMA patients. Neuromuscul Disord. 2014 Apr;24(4):347-52. Epub 2014 Jan 16. PMID: 24491485

281. Lynn S, Aartsma-Rus A, Bushby K, Furlong P, Goemans N, De Luca A, Mayhew A, McDonald C, Mercuri E, Muntoni F, Pohlschmidt M, Verschuuren J, Voit T, Vroom E, Wells DJ, Straub V. Measuring clinical effectiveness of medicinal products for the treatment of Duchenne muscular dystrophy. Neuromuscul Disord. 2015 Jan;25(1):96-105. Epub 2014 Sep 11. PMID: 25307856

282. van Ruiten HJ, Straub V, Bushby K, Guglieri M. Improving recognition of Duchenne muscular dystrophy: a retrospective case note review. Arch Dis Child. 2014 Dec;99(12):1074-7. Epub 2014 Sep 3. PMID: 25187493

283. Chaouch A, Brennan KM, Hudson J, Longman C, McConville J, Morrison PJ, Farrugia ME, Petty R, Stewart W, Norwood F, Horvath R, Chinnery PF, Costigan D, Winer J, Polvikoski T, Healy E, Sarkozy A, Evangelista T, Pogoryelova O, Eagle M, Bushby K, Straub V, Lochmüller H. Two recurrent mutations are associated with GNE myopathy in the North of Britain. J Neurol Neurosurg Psychiatry. 2014 Dec;85(12):1359-65. Epub 2014 Apr 2. PMID: 24695763

284. Haberlova J, Mitrović Z, Zarković K, Lovrić D, Barić V, Berlengi L, Bilić K, Fumić K, Kranz K, Huebner A, von der Hagen M, Barresi R, Bushby K, Straub V, Barić I, Lochmüller H. Psycho-organic symptoms as early manifestation of adult onset POMT1-related limb girdle muscular dystrophy. Neuromuscul Disord. 2014 Nov;24(11):990-2. Epub 2014 Jul 3. PMID:25088310

285. Aartsma-Rus A, Ferlini A, Goemans N, Pasmooij AM, Wells DJ, Bushby K, Vroom E, Balabanov P. Translational and regulatory challenges for exon skipping therapies. Hum Gene Ther. 2014 Oct;25(10):885-92. Review. PMID: 25184444

286. Bushby K, Finkel R, Wong B, Barohn R, Campbell C, Comi GP, Connolly AM, Day JW, Flanigan KM, Goemans N, Jones KJ, Mercuri E, Quinlivan R, Renfroe JB, Russman B, Ryan MM, Tulinius M, Voit T, Moore SA, Lee Sweeney H, Abresch RT, Coleman KL, Eagle M, Florence J, Gappmaier E, Glanzman AM, Henricson E, Barth J, Elfring GL, Reha A, Spiegel RJ, O'donnell MW, Peltz SW, Mcdonald CM; PTC124-GD-007-DMD STUDY GROUP. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve. 2014 Oct;50(4):477-87. PMID:25042182

287. Landfeldt E, Lindgren P, Bell CF, Schmitt C, Guglieri M, Straub V, Lochmüller H, Bushby K. The burden of Duchenne muscular dystrophy: an international, cross-sectional study. Neurology. 2014 Aug 5;83(6):529-36. Epub 2014 Jul 2. PMID: 24991029

288. Thompson R, Johnston L, Taruscio D, Monaco L, Béroud C, Gut IG, Hansson MG, 't Hoen PB, Patrinos GP, Dawkins H, Ensini M, Zatloukal K, Koubi D, Heslop E, Paschall JE, Posada M, Robinson PN, Bushby K, Lochmüller H. RD-Connect: an integrated platform connecting databases, registries, biobanks and clinical

29 | P a g e bioinformatics for rare disease research. J Gen Intern Med. 2014 Aug;29 Suppl 3:S780-7. Review. PMID: 25029978

289. Lamont PJ, Wallefeld W, Hilton-Jones D, Udd B, Argov Z, Barboi AC, Bonneman C, Boycott KM, Bushby K, Connolly AM, Davies N, Beggs AH, Cox GF, Dastgir J, DeChene ET, Gooding R, Jungbluth H, Muelas N, Palmio J, Penttilä S, Schmedding E, Suominen T, Straub V, Staples C, Van den Bergh PY, Vilchez JJ, Wagner KR, Wheeler PG, Wraige E, Laing NG. Novel mutations widen the phenotypic spectrum of slow skeletal/β-cardiac myosin (MYH7) distal myopathy. Hum Mutat. 2014 Jul;35(7):868-79. Epub 2014 May 21. PMID:24664454

290. Ayoglu B, Chaouch A, Lochmüller H, Politano L, Bertini E, Spitali P, Hiller M, Niks EH, Gualandi F, Pontén F, Bushby K, Aartsma-Rus A, Schwartz E, Le Priol Y, Straub V, Uhlén M, Cirak S, 't Hoen PA, Muntoni F, Ferlini A, Schwenk JM, Nilsson P, Al-Khalili Szigyarto C. Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies. EMBO Mol Med. 2014 Jun 11;6(7):918-36. PMID: 24920607

291. Evangelista T, van Engelen B, Bushby K. 200th ENMC International Workshop "European reference networks: recommendations and criteria in the neuromuscular field", 18-20 October 2013, Naarden, The Netherlands. Neuromuscul Disord. 2014 Jun;24(6):537-45. Epub 2014 Mar 15. PMID: 24731389

292. Connolly AM, Florence JM, Cradock MM, Eagle M, Flanigan KM, McDonald CM, Karachunski PI, Darras BT, Bushby K, Malkus EC, Golumbek PT, Zaidman CM, Miller JP, Mendell JR; MDA DMD Clinical Research Network. One year outcome of boys with Duchenne muscular dystrophy using the Bayley-III scales of infant and toddler development. Pediatr Neurol. 2014 Jun;50(6):557-63 Epub 2014 Feb 15. PMID: 24842254

293. Barresi R, Morris C, Hudson J, Curtis E, Pickthall C, Bushby K, Davies NP, Straub V. Conserved expression of truncated telethonin in a patient with limb-girdle muscular dystrophy 2G. Neuromuscul Disord. 2015 Apr;25(4):349-52. Epub 2014 Dec 24. PMID: 25724973

294. van den Bergen JC, Hiller M, Böhringer S, Vijfhuizen L, Ginjaar HB, Chaouch A, Bushby K, Straub V, Scoto M, Cirak S, Humbertclaude V, Claustres M, Scotton C, Passarelli C, Lochmüller H, Muntoni F, Tuffery-Giraud S, Ferlini A, Aartsma-Rus AM, Verschuuren JJ, 't Hoen PA, Spitali P. Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants. J Neurol Neurosurg Psychiatry. 2015 Oct;86(10):1060-5. Epub 2014 Dec 4. PMID: 25476005

295. Burch PM, Pogoryelova O, Goldstein R, Bennett D, Guglieri M, Straub V, Bushby K, Lochmüller H, Morris C. Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy. J Neuromuscul Dis. 2015 Sep 2;2(3):241-255. PMID: 26870665

296. Belaya K, Rodríguez Cruz PM, Liu WW, Maxwell S, McGowan S, Farrugia ME, Petty R, Walls TJ, Sedghi M, Basiri K, Yue WW, Sarkozy A, Bertoli M, Pitt M, Kennett R, Schaefer A, Bushby K, Parton M, Lochmüller H, Palace J, Muntoni F, Beeson D. Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies. Brain. 2015 Sep;138(Pt 9):2493-504. Epub 2015 Jun 30. PMID: 26133662

297. Rahbek J, Steffensen BF, Bushby K, de Groot IJ. 206th ENMC International

30 | P a g e Workshop: Care for a novel group of patients - adults with Duchenne muscular dystrophy Naarden, The Netherlands, 23-25 May 2014. Neuromuscul Disord. 2015 Sep;25(9):727-38. Epub 2015 May 27. PMID: 26099652

298. Wood CL, Straub V, Guglieri M, Bushby K, Cheetham T. Short stature and pubertal delay in Duchenne muscular dystrophy. Arch Dis Child. 2016 Jan;101(1):101-6. Epub 2015 Jul 3. Review. PMID: 26141541

299. Landfeldt E, Mayhew A, Eagle M, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, Bushby K. Development and psychometric analysis of the Duchenne muscular dystrophy Functional Ability Self-Assessment Tool (DMDSAT). Neuromuscul Disord. 2015 Dec;25(12):937-44. Epub 2015 Sep 26.Erratum in: Neuromuscul Disord. 2016 Apr-May;26(4-5):329. PMID: 26483273

300. Kinnett K, Rodger S, Vroom E, Furlong P, Aartsma-Rus A, Bushby K. Imperatives for DUCHENNE MD: a Simplified Guide to Comprehensive Care for Duchenne Muscular Dystrophy. PLoS Curr. 2015 Aug 7;7. PMID: 26331093

301. Evangelista T, Bansagi B, Pyle A, Griffin H, Douroudis K, Polvikoski T, Antoniadi T, Bushby K, Straub V, Chinnery PF, Lochmüller H, Horvath R. Phenotypic variability of TRPV4 related neuropathies. Neuromuscul Disord. 2015 Jun;25(6):516-21. Epub 2015 Mar 18. PMID: 25900305

302. Heslop E, Csimma C, Straub V, McCall J, Nagaraju K, Wagner KR, Caizergues D, Korinthenberg R, Flanigan KM, Kaufmann P, McNeil E, Mendell J, Hesterlee S, Wells DJ, Bushby K; TACT. The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development. Orphanet J Rare Dis. 2015 Apr 23;10:49. Review. PMID:25902795

303. Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K, Dawkins H, Lamont L, Roy AJ, Chamova T, Guergueltcheva V, Chan S, Korngut L, Campbell C, Dai Y, Wang J, Barišić N, Brabec P, Lahdetie J, Walter MC, Schreiber-Katz O, Karcagi V, Garami M, Viswanathan V, Bayat F, Buccella F, Kimura E, Koeks Z, van den Bergen JC, Rodrigues M, Roxburgh R, Lusakowska A, Kostera-Pruszczyk A, Zimowski J, Santos R, Neagu E, Artemieva S, Rasic VM, Vojinovic D, Posada M, Bloetzer C, Jeannet PY, Joncourt F, Díaz-Manera J, Gallardo E, Karaduman AA, Topaloğlu H, El Sherif R, Stringer A, Shatillo AV, Martin AS, Peay HL, Bellgard MI, Kirschner J, Flanigan KM, Straub V, Bushby K, Verschuuren J, Aartsma-Rus A, Béroud C, Lochmüller H. The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mutat. 2015 Apr;36(4):395-402. Epub 2015 Mar 17. PMID: 25604253

304. Rodger S, Woods KL, Bladen CL, Stringer A, Vry J, Gramsch K, Kirschner J, Thompson R, Bushby K, Lochmüller H. Adult care for Duchenne muscular dystrophy in the UK. J Neurol. 2015 Mar;262(3):629-41. Epub 2014 Dec 24. PMID: 25536903

305. Landfeldt E, Lindgren P, Bell CF, Schmitt C, Guglieri M, Straub V, Lochmüller H, Bushby K. Compliance to Care Guidelines for Duchenne Muscular Dystrophy. J Neuromuscul Dis. 2015;2(1):63-72. PMID: 26870664

306. Wood CL, Cheetham TD, Guglieri M, Bushby K, Owen C, Johnstone H, Straub V. Testosterone Treatment of Pubertal Delay in Duchenne Muscular Dystrophy. Neuropediatrics. 2015 Dec;46(6):371-6. Epub 2015 Sep 26. PMID: 26408798

307. Palmio J, Jonson PH, Evilä A, Auranen M, Straub V, Bushby K, Sarkozy A,

31 | P a g e Kiuru-Enari S, Sandell S, Pihko H, Hackman P, Udd B. Novel mutations in DNAJB6 gene cause a very severe early-onset limb-girdle muscular dystrophy 1D disease. Neuromuscul Disord. 2015 Nov;25(11):835-42. Epub 2015 Jul 27. PMID: 26338452

308. Palmio J, Evilä A, Bashir A, Norwood F, Viitaniemi K, Vihola A, Huovinen S, Straub V, Hackman P, Hirano M, Bushby K, Udd B. Re-evaluation of the phenotype caused by the common MATR3 p.Ser85Cys mutation in a new family. J Neurol Neurosurg Psychiatry. 2016 Apr;87(4):448-50. Epub 2015 May 7. PMID: 25952333

309. Landfeldt E, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, Bushby K. Health-related quality of life in patients with Duchenne muscular dystrophy: a multinational, cross-sectional study. Dev Med Child Neurol. 2016 May;58(5):508-15. Epub 2015 Oct 19. PMID: 26483095

310. Figueroa-Bonaparte S, Hudson J, Barresi R, Polvikoski T, Williams T, Töpf A, Harris E, Hilton-Jones D, Petty R, Willis TA, Longman C, Dougan CF, Parton MJ, Hanna MG, Quinlivan R, Farrugia ME, Guglieri M, Bushby K, Straub V, Lochmüller H, Evangelista T. Mutational spectrum and phenotypic variability of VCP-related neurological disease in the UK. J Neurol Neurosurg Psychiatry. 2016 Jun;87(6):680-1. Epub 2015 Jun 23. PMID: 26105173

311. Willis TA, Wood CL, Hudson J, Polvikoski T, Barresi R, Lochmüller H, Bushby K, Straub V. Muscle hypertrophy as the presenting sign in a patient with a complete FHL1 deletion. Clin Genet. 2016 Aug;90(2):166-70. Epub 2016 Jan 8. PMID: 27409453

312. Harris E, Bladen CL, Mayhew A, James M, Bettinson K, Moore U, Smith FE, Rufibach L, Cnaan A, Bharucha-Goebel DX, Blamire AM, Bravver E, Carlier PG, Day JW, Díaz-Manera J, Eagle M, Grieben U, Harms M, Jones KJ, Lochmüller H, Mendell JR, Mori-Yoshimura M, Paradas C, Pegoraro E, Pestronk A, Salort-Campana E, Schreiber-Katz O, Semplicini C, Spuler S, Stojkovic T, Straub V, Takeda S, Rocha CT, Walter MC, Bushby K; Jain COS Consortium. The Clinical Outcome Study for dysferlinopathy: An international multicenter study. Neurol Genet. 2016 Aug 4;2(4):e89. eCollection 2016 Aug. PMID: 27602406

313. Scalco RS, Gardiner AR, Pitceathly RD, Hilton-Jones D, Schapira AH, Turner C, Parton M, Desikan M, Barresi R, Marsh J, Manzur AY, Childs AM, Feng L, Murphy E, Lamont PJ, Ravenscroft G, Wallefeld W, Davis MR, Laing NG, Holton JL, Fialho D, Bushby K, Hanna MG, Phadke R, Jungbluth H, Houlden H, Quinlivan R. CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies. Neuromuscul Disord. 2016 Aug;26(8):504-10. Epub 2016 May 11. PMID: 27312022

314. Van Ruiten HJ, Marini Bettolo C, Cheetham T, Eagle M, Lochmuller H, Straub V, Bushby K, Guglieri M. Why are some patients with Duchenne muscular dystrophy dying young: An analysis of causes of death in North East England. Eur J Paediatr Neurol. 2016 Jul 30. [Epub ahead of print] PMID: 27524390

315. Mitzelfelt KA, Limphong P, Choi MJ, Kondrat FD, Lai S, Kolander KD, Kwok WM, Dai Q, Grzybowski MN, Zhang H, Taylor GM, Lui Q, Thao MT, Hudson JA, Barresi R, Bushby K, Jungbluth H, Wraige E, Geurts AM, Benesch JL, Riedel M, Christians ES, Minella AC, Benjamin IJ. The Human 343delT HSPB5 Chaperone Associated with Early-onset Skeletal Myopathy Causes Defects in Protein Solubility. J Biol Chem. 2016 Jul 15;291(29):14939-53. Epub 2016 May 19. PMID: 27226619

316. Pohjola P, Hedley V, Bushby K, Kääriäinen H. Challenges raised by cross-border

32 | P a g e testing of rare diseases in the European union. Eur J Hum Genet. 2016 Jul 6. Epub ahead of print] PMID: 27381091

317. Straub V, Balabanov P, Bushby K, Ensini M, Goemans N, De Luca A, Pereda A, Hemmings R, Campion G, Kaye E, Arechavala-Gomeza V, Goyenvalle A, Niks E, Veldhuizen O, Furlong P, Stoyanova-Beninska V, Wood MJ, Johnson A, Mercuri E, Muntoni F, Sepodes B, Haas M, Vroom E, Aartsma-Rus A. Stakeholder cooperation to overcome challenges in orphan medicine development: the example of Duchenne muscular dystrophy. Lancet Neurol. 2016 Jul;15(8):882-90. Review. PMID: 27302365

318. Srinivasan R, Rawlings D, Wood CL, Cheetham T, Moreno AC, Mayhew A, Eagle M, Guglieri M, Straub V, Owen C, Bushby K, Sarkozy A. Prophylactic oral bisphosphonate therapy in duchenne muscular dystrophy. Muscle Nerve. 2016 Jun;54(1):79-85. Epub 2016 Apr 27. PMID: 26599341

319. Landfeldt E, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, Bushby K. Quantifying the burden of caregiving in Duchenne muscular dystrophy. J Neurol. 2016 May;263(5):906-15. Epub 2016 Mar 10. PMID: 26964543

320. Scotton C, Bovolenta M, Schwartz E, Falzarano MS, Martoni E, Passarelli C, Armaroli A, Osman H, Rodolico C, Messina S, Pegoraro E, D'Amico A, Bertini E, Gualandi F, Neri M, Selvatici R, Boffi P, Maioli MA, Lochmüller H, Straub V, Bushby K, Castrignanò T, Pesole G, Sabatelli P, Merlini L, Braghetta P, Bonaldo P, Bernardi P, Foley R, Cirak S, Zaharieva I, Muntoni F, Capitanio D, Gelfi C, Kotelnikova E, Yuryev A, Lebowitz M, Zhang X, Hodge BA, Esser KA, Ferlini A. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy. J Cell Sci. 2016 Apr 15;129(8):1671-84. Epub 2016 Mar 4. PMID: 26945058

321. Landfeldt E, Mayhew A, Eagle M, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, Bushby K. Corrigendum to "Development and psychometric analysis of the Duchenne muscular dystrophy Functional Ability Self-Assessment Tool (DMDSAT)" [Neuromuscular Disorders 25 (2015) 937-944]. Neuromuscul Disord. 2016 Apr-May;26(4- 5):329. Epub 2016 Mar 14. PMID: 27087611

323. Aartsma-Rus A, Ginjaar IB, Bushby K. The importance of genetic diagnosis for Duchenne muscular dystrophy. J Med Genet. 2016 Mar;53(3):145-51. Epub 2016 Jan 11. Review. PMID: 26754139

324. Evangelista T, Hedley V, Atalaia A, Johnson M, Lynn S, Le Cam Y, Bushby K. The context for the thematic grouping of rare diseases to facilitate the establishment of European Reference Networks. Orphanet J Rare Dis. 2016 Feb 24;11:17. PMID: 26911987

Doug Turnbull

325. Alston CL, Schaefer AM, Raman P, Solaroli N, Krishnan KJ, Blakely EL, He L, Craig K, Roberts M, Nixon J, Horvat R, Turnbull DM, Karlsson A, Gorman GS, Taylor RW. Late- onset respiratory failure due to TK2 mutations causing multiple mtDNA deletions. Neurology 81(23) 2051-3. Dec 2013. PMID: 24198295

326. Spendiff S. Reza M. Murphy JL. Gorman G. Blakely EL. Taylor RW. Horvath R. Campbell G. Newman J. Lochmüller H. Turnbull DM. Mitochondrial DNA deletions in

33 | P a g e muscle satellite cells: implications for therapies. Human Molecular Genetics 22(23) 4739-47. Dec 2013 PMID: 23847047

327. Yu-Wai-Man C. Smith FE. Firbank MJ. Guthrie G. Guthrie S. Gorman GS. Taylor RW. Turnbull DM. Griffiths PG. Blamire AM. Chinnery PF. Yu-Wai-Man P. Extraocular muscle atrophy and central nervous system involvement in chronic progressive external ophthalmoplegia. PLoS One 8(9): e75048. 2013. PMID: 24086434

328. Picard M. Gentil BJ. McManus MJ. White K. St Louis K. Gartside SE. Wallace DC. Turnbull DM. Acute exercise remodels mitochondrial membrane interactions in mouse skeletal muscle. Journal of Applied Physiology. 115(10):1562-71 Nov 2013 PMID: 23970537

329. Schaefer AM, Walker M, Turnbull DM, Taylor RW. Endocrine disorders in mitochondrial disease. Molecular and Cellular Endocrinology 379 (1-2) 2-11 Oct 2013. PMID: 23769710

330. Bates MG. Newman JH. Jakovljevic DG. Hollingsworth KG. Alston CL. Zalewski P. Klawe JJ. Blamire AM. MacGowan GA. Keavney BD. Bourke JP. Schaefer A. McFarland R. Newton JL. Turnbull DM. Taylor RW. Trenell MI. Gorman GS. Defining cardiac adaptations and safety of endurance training in patients with m.3243A>G-related mitochondrial disease. International Journal of Cardiology 168(4) 3599-608 Oct 2013 PMID: 23742928

331. Pfeffer G, Horvath R, Klopstock T, Mootha VK, Suomalainen A, Koene S, Hirano M, Zeviani M, Bindoff LA, Yu-Wai-Man P, Hanna M, Carelli V, McFarland R, Majamaa K, Turnbull DM, Smeitink J, Chinnery PF. New treatments for mitochondrial disease-no time to drop our standards. [Review]. Nature Reviews Neurology Aug 2013. PMID: 23817350

332. G R Campbell, A Reeve, I Ziabreva, T M Polvikoski, R W Taylor, R Reynolds, DM Turnbull, D J Mahad. Mitochondrial DNA deletions and depletion within paraspinal muscles. Neuropathology and applied neurobiology Jun 2013. PMID: 22762368

333. Emma L Blakely, John W Yarham, Charlotte L Alston, Kate Craig, Joanna Poulton, Charlotte Brierley, Soo-Mi Park, Andrew Dean, John H Xuereb, Kirstie N Anderson, Alistair Compston, Chris Allen, Saba Sharif, Peter Enevoldson, Martin Wilson, Simon R Hammans, Douglass M Turnbull, Robert McFarland, Robert W Taylor. Pathogenic mitochondrial tRNA point mutations: nine novel mutations affirm their importance as a cause of mitochondrial disease. Human mutation. May 2013. PMID: 23696415

334. JL Elson, M Cadogan, S Apabhai, RG Whittaker, A Phillips, MI Trennell, R Horvath, RW Taylor, R McFarland, E McColl, DM Turnbull, G S Gorman. Initial development and validation of a mitochondrial disease quality of life scale. Neuromuscular disorders: NMD Apr 2013. PMID: 23433484

335. Roger G Whittaker, Elizabeth Hall, Muhammad K Mansoor, Robert W Taylor, Douglass M Turnbull. Incidence of carpal tunnel syndrome in adult patients with mitochondrial disease. Journal of the peripheral nervous system. JPNS Mar 2013. PMID: 23521646

336. Picard M, Turnbull D. Linking the metabolic state and mitochondrial DNA in chronic disease, health, and aging. Diabetes Mar 2013. PMID: 23431006

337. Nichola Z Lax, Sharmilee Gnanapavan, Sarah J Dowson, Charlotte L Alston, Langping He, Tuomo M Polvikoski, Evelyn Jaros, Dominic G O'Donovan, John W Yarham, Douglass

34 | P a g e M Turnbull, Andrew F Dean, Robert W Taylor. Early-onset cataracts, spastic paraparesis, and ataxia caused by a novel mitochondrial tRNAGlu (MT-TE) gene mutation causing severe complex I deficiency: a clinical, molecular, and neuropathologic study. Journal of neuropathology and experimental neurology Feb 2013. PMID: 23334599

338. John W Yarham, Emma L Blakely, Charlotte L Alston, Mark E Roberts, John Ealing, Piyali Pal, Douglass M Turnbull, Robert McFarland, Robert W Taylor. The m.3291T>C mt-tRNA(Leu(UUR)) mutation is definitely pathogenic and causes multisystem mitochondrial disease. Journal of the neurological sciences Feb 2013. PMID: 23273904

339. Grady JP, Murphy JL, Blakely EL, Haller RG, Taylor RW, Turnbull DM, Tuppen HA. Accurate measurement of mitochondrial DNA deletion level and copy number differences in human skeletal muscle. PLoS One. 2014 Dec 4;9(12):e114462. PMID: 25474153

340. Nesbitt V, Alston CL, Blakely EL, Fratter C, Feeney CL, Poulton J, Brown GK, Turnbull DM, Taylor RW, McFarland R. A national perspective on prenatal testing for mitochondrial disease. Eur J Hum Genet. 2014. Nov;22(11):1255-9. PMID: 24642831

341. Greaves LC, Nooteboom M, Elson JL, Tuppen HA, Taylor GA, Commane DM, Arasaradnam RP, Khrapko K, Taylor RW, Kirkwood TB, Mathers JC, Turnbull DM. Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing. PLoS Genet. 2014 Sep 18;10(9):e1004620. PMID: 25232829

342. Rygiel KA, Grady JP, Turnbull DM. Respiratory chain deficiency in aged spinal motor neurons. Neurobiol Aging. 2014. Oct;35(10):2230-8. PMID: 24684792

343. Campbell G, Krishnan KJ, Deschauer M, Taylor RW, Turnbull DM. Dissecting the mechanisms underlying the accumulation of mitochondrial DNA deletions in human skeletal muscle. Hum Mol Genet. 2014. Sep 1;23(17):4612-20 PMID: 24740879

344. Rygiel KA, Miller J, Grady JP, Rocha MC, Taylor RW, Turnbull DM. Mitochondrial and inflammatory changes in sporadic inclusion body myositis. Neuropathol Appl Neurobiol. 2015. Apr;41(3):288-303. PMID: 24750247

345. Blakely EL, Alston CL, Lecky B, Chakrabarti B, Falkous G, Turnbull DM, Taylor RW, Gorman GS. Distal weakness with respiratory insufficiency caused by the m.8344A > G "MERRF" mutation. Neuromuscul Disord. 2014 Jun;24(6):533-6. PMID: 24792523

346. Grünewald A, Lax NZ, Rocha MC, Reeve AK, Hepplewhite PD, Rygiel KA, Taylor RW, Turnbull DM. Quantitative quadruple-label immunofluorescence of mitochondrial and cytoplasmic proteins in single neurons from human midbrain tissue. J Neurosci Methods. 2014 Jul 30;232:143-9. PMID: 24880043

347. Baines HL, Stewart JB, Stamp C, Zupanic A, Kirkwood TB, Larsson NG, Turnbull DM, Greaves LC. Similar patterns of clonally expanded somatic mtDNA mutations in the colon of heterozygous mtDNA mutator mice and ageing humans. Mech Ageing Dev. 2014 Jul;139:22-30. PMID: 24915468

348. Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski- Feder E, Abicht A, Czermin B, Kleinle S, Morris AA, Vassallo G, Gorman GS, Ramesh V, Turnbull DM, Santibanez-Koref M, McFarland R, Horvath R, Chinnery PF. Use of whole- exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA. 2014 Jul 2;312(1):68-77. PMID: 25058219

35 | P a g e 349. Pfeffer G. Gorman GS. Griffin H. Kurzawa-Akanbi M. Blakely EL. Wilson I. Sitarz K. Moore D. Murphy JL. Alston CL. Pyle A. Coxhead J. Payne B. Gorrie GH. Longman C. Hadjivassiliou M. McConville J. Dick D. Imam I. Hilton D. Norwood F. Baker MR. Jaiser SR. Yu-Wai-Man P. Farrell M. McCarthy A. Lynch T. McFarland R. Schaefer AM. Turnbull DM. Horvath R. Taylor RW. Chinnery PF. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance Brain. 2014. 137 (5) 1323-36 May-14. PMID: 24727571

350. Chinnery PF, Craven L, Mitalipov S, Stewart JB, Herbert M, Turnbull DM. The challenges of mitochondrial replacement PLoS Genetics. 2014. 10(4) e1004315 Apr-14 PMID: 24762741

351. Baines HL, Turnbull DM, Greaves LC. Human stem cell ageing: do mitochondrial DNA mutations have a causal role? Aging Cell. 2014. 13(2) 201-5 Apr-14. PMID: 24382254

352. Galna B. Newman J. Jakovljevic DG. Bates MG. Schaefer AM. McFarland R. Turnbull DM. Trenell MI. Gorman GS. Rochester L. Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences. Journal of Neurology. 2014. 261(1) 73-82. Jan-14. PMID: 24150688

353. Campbell G, Krishnan KJ, Deschauer M, Taylor RW, Turnbull DM. Dissecting the mechanisms underlying the accumulation of mitochondrial DNA deletions in human skeletal muscle. Human Molecular Genetics. 2014. PMID: 24740879

354. Nesbitt V, Alston CL, Blakely EL, Fratter C, Feeney CL, Poulton J, Brown GK, Turnbull DM, Taylor RW, McFarland R. A national perspective on prenatal testing for mitochondrial disease. European Journal of Human Genetics. 2014. Nov, 22(11)::1255-9. PMID: 24642831

355. Blakely EL, Alston CL, Lecky B, Falkous G, Turnbull DM, Taylor RW, Gorman GS distal weakness with respiratory insufficiency caused by the m.8344A>G "MERFF" mutation. Neuromuscular Disorders 24, 533-536. 2014. PMID: 24792523

356. Gorman GS, Pfeffer G, Griffin HR, Blakely EL, Kurzawa-Akanbi M, Gabriel J, Sitarz K, Roberts M, Schoser B, Pyle A, Schaefer AM, McFarland R, Turnbull DM, Horvath R, Chinnery PF, Taylor RW. Clonal expansion of secondary mtDNA deletions associated with spinocerebellar ataxia type 28. JAMA Neurology. 2014. PMID: 25420100

357. Grady JP, Campbell G, Ratnaike T, Blakely EL, Falkous G, Nesbitt V, Schaefer AM, McNally RJ, Gorman GS, Taylor RW, Turnbull DM, McFarland R. Disease progression in patients with isngle, large-scale mitochondrial DNA deletions. Brain. 2014. 137 (2) 323-334. Feb. PMID: 24277717

358. Greggains GD. Lister LM. Tuppen HA. Zhang Q. Needham LH. Prathalingam N. Hyslop LA. Craven L. Polanski Z. Murdoch AP. Turnbull DM. Herbert M. Therapeutic potential of somatic cell nuclear transfer for degenerative disease caused by mitochondrial DNA mutations. Science Reporter 4, 3844. 2014. PMID: 24457623

359. *Hall AM, Vilasi A, Garcia-Perez I, Lapsley M, Alston CL, Pitceathly RD, McFarland R, Schaefer AM, Turnbull DM, Beaumont NJ, Hsuan JJ, Cutillas PR, Lindon JC, Holmes E, Unwin RJ, Taylor RW, Gorman GS, Rahman S, Hanna MG. The urinary proteome and metabonome differ from normal in adults with mitochondrial disease. Kidney Int. 2015 Mar;87(3):610-22. PMID: 25207879

36 | P a g e 360. Richardson J, Irving L, Hyslop LA, Choudhary M, Murdoch A, Turnbull DM, Herbert M. Concise reviews: Assisted reproductive technologies to prevent transmission of mitochondrial DNA disease. Stem Cells. 2015 Mar;33(3):639-45. PMID: 25377180

361. Gorman GS, Pfeffer G, Griffin H, Blakely EL, Kurzawa-Akanbi M, Gabriel J, Sitarz K, Roberts M, Schoser B, Pyle A, Schaefer AM, McFarland R, Turnbull DM, Horvath R, Chinnery PF, Taylor RW. Clonal expansion of secondary mitochondrial DNA deletions associated with spinocerebellar ataxia type 28. JAMA Neurol. 2015 Jan;72(1):106-11. PMID: 25420100

362. Gorman GS, Blakely EL, Hornig-Do HT, Tuppen HA, Greaves LC, He L, Baker A, Falkous G, Newman J, Trenell MI, Lecky B, Petty RK, Turnbull DM, McFarland R, Taylor RW. Novel MTND1 mutations cause isolated exercise intolerance, complex I deficiency and increased assembly factor expression. Clin Sci (Lond). 2015 Jun;128(12):895-904. PMID: 25626417

363. Gorman GS, Grady JP, Ng Y, Schaefer AM, McNally RJ, Chinnery PF, Yu-Wai-Man P, Herbert M, Taylor RW, McFarland R, Turnbull DM. Mitochondrial donation--how many women could benefit? N Engl J Med. 2015 Feb 26;372(9):885-7. PMID: 25629662

364. Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, Taylor RW, Turnbull DM, McFarland R. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015 May;77(5):753-9. PMID: 25652200

365. Turnbull DM, Rustin P. Genetic and biochemical intricacy shapes mitochondrial cytopathies. Neurobiol Dis. 2015 Feb 12. PMID: 25684538

366. Lax NZ, Grady J, Laude A, Chan F, Hepplewhite PD, Gorman G, Whittaker RG, Ng Y, Cunningham MO, Turnbull DM. Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease. Neuropathol Appl Neurobiol. 2015 Mar 18. PMID: 25786813

367. Stoll EA, Makin R, Sweet IR, Trevelyan AJ, Miwa S, Horner PJ, Turnbull DM. Neural Stem Cells in the Adult Subventricular Zone Oxidize Fatty Acids to Produce Energy and Support Neurogenic Activity. Stem Cells. 2015 Jul;33(7):2306-19. PMID: 25919237

368. Rygiel KA, Grady JP, Taylor RW, Tuppen HA, Turnbull DM. Triplex real-time PCR--an improved method to detect a wide spectrum of mitochondrial DNA deletions in single cells. Sci Rep. 2015 May 19;5:9906 PMID: 25989140

369. Gorman GS, Elson JL, Newman J, Payne B, McFarland R, Newton JL, Turnbull DM. Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease. Neuromuscul Disord. 2015 Jul;25(7):563-6. PMID: 26031904

370. Reeve AK, Ludtmann MH, Angelova PR, Simcox EM, Horrocks MH, Klenerman D, Gandhi S, Turnbull DM, Abramov AY. Aggregated α-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons. Cell Death Dis. 2015 Jul 16;6:e1820. PMID: 26181201

371. Ng YS, Grady JP, Lax NZ, Bourke JP, Alston CL, Hardy SA, Falkous G, Schaefer AG, Radunovic A, Mohiddin SA, Ralph M, Alhakim A, Taylor RW, McFarland R, Turnbull DM, Gorman GS. Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults. Eur Heart J. 2015 Jul 17. PMID: 26188002

37 | P a g e 372. Rygiel KA, Miller J, Grady JP, Rocha MC, Taylor RW, Turnbull DM. Mitochondrial and inflammatory changes in sporadic Inclusion Body Myositis. Neuropathology and Applied Neurobiology. 2015. Apr;41(3):288-303. PMID: 24750247

373. Lax NZ, Grady J, Laude A, Chan F, Hepplewhite PD, Gorman G, Whittaker RG, Ng Y, Cunningham MO, Turnbull DM. Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease. Neuropathology and Applied Neurobiology 2016, 42(2), 180-193. PMID: 25786813

374. Ng YS, Turnbull DM. Mitochondrial disease: genetics and management. Journal of Neurology 2016, 263(1), 179-191. PMID: 26315846

375. Chan F, Lax NZ, Davies CH, Turnbull DM, Cunningham MO. Neuronal oscillations: a physiological correlate for targeting mitochondrial dysfunction in neurodegenerative diseases?. Neuropharmacology 2016, 102, 48-58. PMID: 26518370

376. Craven L, Herbert M, Murdoch A, Murphy J, Davies JL, Turnbull DM. Research into Policy: A Brief History of Mitochondrial Donation. Stem Cells 2016, 34(2), 265-267. PMID: 26418557

377. Rygiel KA, Picard M, Turnbull DM. The ageing neuromuscular system and sarcopenia - A mitochondrial perspective. The Journal of Physiology. 2016. PMID: 26921061

378. Phillips J, Laude A, Lightowlers R, Morris CM, Turnbull DM, Lax NZ. Development of passive CLARITY and immunofluorescent labelling of multiple proteins in human cerebellum: understanding mechanisms of neurodegeneration in mitochondrial disease. Sci Rep. 2016 May 16;6:26013. PMID: 27181107

379. Rygiel KA, Tuppen HA, Grady JP, Vincent A, Blakely EL, Reeve AK, Taylor RW, Picard M, Miller J, Turnbull DM. Complex mitochondrial DNA rearrangements in individual cells from patients with sporadic inclusion body myositis. Nucleic Acids Res. 2016 Apr 30. [Epub ahead of print] PMID: 27131788

380. Martikainen MH, Ng YS, Gorman GS, Alston CL, Blakely EL, Schaefer AM, Chinnery PF, Burn DJ, Taylor RW, McFarland R, Turnbull DM. Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease. JAMA Neurol. 2016 Apr 25. [Epub ahead of print] PMID: 27111573

381. Russell OM, Lightowlers RN, Turnbull DM. Applying the Airbrakes: Treating Mitochondrial Disease with Hypoxia. Mol Cell. 2016 Apr 7;62(1):5-6. PMID: 27058784

Chris Clark

382. “The Sensitivity of the diffusion-weighted MRI signal decay curve to microstructural changes due to Duchenne Muscular Dystrophy” Matt G Hall and Chris A Clark Proceedings of the Ninth UK Neuromuscular Translational Research Conference (2016), P25

383. "Fractional diffusion as a probe of microstructural change in a mouse model of Duchenne Muscular Dystrophy” Matt G Hall, Paola Porcari, Andrew Blamire, and Chris A Clark Proceedings of the Ninth UK Neuromuscular Translational Research Conference (2016), P26

38 | P a g e 384. "Fractional diffusion as a probe of microstructural change in a mouse model of Duchenne Muscular Dystrophy" Matt G Hall, Paola Porcari, Andrew Blamire, and Chris A Clark Proceedings of the 16th Annual Meeting of the International Society for Magnetic Resonance in Medicine, Singapore (2016), 1981

385. "Diffusion in Hierarchical systems: a simulation study in healthy and diseased muscle tissue" Matt G Hall and Chris A Clark Magnetic Resonance in Medicine (submitted)

Giulio Cossu

386. Godi C, Ambrosi A, Nicastro MF, Previtali SC, Santarosa C, Napolitano S, Natali Sora MG, Tettamanti A, Gerevini S, Cicalese MP, Sitzia C, Venturini M, Falini A, Gatti R, Ciceri F, Cossu G, Torrente Y, Politi LS. 2016. MRI Longitudinal Quantification of Muscle Degeneration in Duchenne Muscular Dystrophy. Annals of Clinical and Translational Neurology. In press.

387. Serena E, Zatti S, Zoso A, Lo Verso F, Tedesco FS, Cossu G, Elvassore N. 2016 Skeletal muscle differentiation on a chip shows human donor mesoangioblasts efficiency in restoring dystrophin in a DMD model. Stem Cell Transl. Med. Aug 8. [Epub ahead of print] PMID: 27502519

388. Sacchetti B, Funari A, Remoli C, Giannicola G, Kogler G, Liedtke S, Cossu G, Serafini M, Sampaolesi M, Tagliafico E, Tenedini I, Saggio I, Robey PG, Riminucci M, Bianco P. 2016. No identical “mesenchymal stem cells” at different times and sites: human committed progenitors of distinct origin and differentiation potential are incorporated as adventitial cells in microvessels. Stem Cell Rep. 6,897-913. PMID: 27304917

389. Cossu G, Buccione R, De Luca M. 2016. A discussion on cell therapy in Manchester. Stem Cell Rep. 16, 614-6. PMID: 27039900

390. Rossi G, Antonini S, Bonfanti C, Monteverde S, Tajbakhsh S, Cossu G, Messina G. 2016. Nfix regulates temporal progression of muscle regeneration through modulation of Myostatin expression. Cell Reports 14, 2338-49. PMID: 26923583

391. Cossu G, Previtali SC, Napolitano S, Cicalese MP, Tedesco FS, Nicastro F, Noviello M, Roostalu U, Natali Sora MG, Scarlato M, De Pellegrin M, Godi C, Giuliani S, Ciotti F, Tonlorenzi R, Lorenzetti I, Rivellini C, Benedetti S, Gatti R, Marktel S, Mazzi B, Tettamanti A, Ragazzi M, Imro MA, Marano G, Ambrosi A, Fiori R, Sormani MP, Bonini C, Venturini M, Politi LS, Torrente Y, Ciceri, F. 2015. Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne Muscular Dystrophy. EMBO Mol. Med. 7,1513-28. PMID: 26543057

392. Fuoco C, Rizzi R, Biondo A, Longa E, Mascaro A, Shapira-Schweitzer K, Kossovar O, Benedetti S, Salvatori ML, Santoleri S, Testa S, Bernardini S, Bottinelli R, Bearzi C, Cannata SM, Seliktar D, Cossu G, Gargioli C. 2015. In vivo generation of a mature and functional artificial skeletal muscle. PMID: 25715804

393. Bonfanti C, Rossi G, Tedesco FS, Giannotta M, Benedetti S, Tonlorenzi R, Antonini S, Marazzi G, Dejana E, Sassoon D, Cossu G, Messina G. 2015. PW1/Peg3 expression regulates the key properties determining mesoangioblast stem cell competence. Nature Comm. 6:6364.

394. *Di Foggia V, Zhang X, Licastro D, Gerli M, Padkhe R, Muntoni F, Mourikis P, Tajbakhsk S, Ellis M, Greaves L, Taylor R, Cossu G, Robson L, Marino S. 2014. Bm1

39 | P a g e enhances skeletal muscle regeneration through MT1 mediated oxidative stress protection in a mouse model of dystrophinopathy. J. Exp. Med. 211:2617-33. PMID: 25452464

395. Noviello M, Tedesco FS, Bondanza A, Tonlorenzi R, Carbone MR, Gerli M, Marktel S, Napolitano S, Cicalese MP, Ciceri F, Peretti G, Cossu G, Bonini C. 2014. Inflammation converts human mesoangioblasts into targets of alloreactive immune responses: implications for allogeneic cell therapy of DMD. Mol. Ther. 22:1342-52. PMID: 24736278

396. Azzoni E, Conti V, Dellavalle A, Campana L, Adams RH, Cossu G, Brunelli S. 2014 Mouse yolk sac VE-Cadherin+ cells generate mesodermal multipotent progenitors that physiologically contribute to several lineages in the embryo and in the growing and regenerating skeletal muscle. Development 141:1821-34.

397. Narayanan G, Cossu G, Galli MC, Flory E, Ovelgonne H, Salmikangas P, Schneider CK, Trouvin JH 2014 Clinical development of gene therapy needs a tailored approach: a regulatory perspective from the EU. Human Gene Ther. Clin. Dev. 25:1-6. PMID: 24649836

398. Giannotta M, Benedetti S, Tedesco FS, Corada M, Trani M, D’Antuono R, Queensta M, Orsenigo F, Galvez BG, Cossu G and Dejana E. 2014 Targeting endothelial Junctional Adhesion Molecule-A/ EPAC/ Rap-1 axis as a novel strategy to increase stem cell engraftment in dystrophic muscles. Embo Mol Med. 6:239-58. PMID: 24378569

399. Aiuti A, Cossu G, de Felipe P, Galli MC, Narayanan A, Renner M, Stahlbom M, Schneider CK, Voltz-Girolt C. 2013. The Committee for Advanced Therapies’ (CAT) reflection paper on management of clinical risks deriving from insertional mutagenesis Hum Gene Ther Clin Dev. 24:47-54. PMID: 23862696

400. Cappellari O & Cossu G. 2013. Pericytes in development and pathology of skeletal muscle. Circ. Res. 113, 341-7. PMID: 23868830

401. Urciuolo A, Valeria Morbidoni A, Gattazzo F, Quarta M, Grumati P, Molon S, Montemurro F, Tedesco FS, Cossu G, Vozzi T, Rando TA, Bonaldo P. 2013. Collagen VI is a key component of satellite cell niche. Nature Comm. Jun 7;4:1964. PMID: 23743995

402. Cappellari O, Benedetti S, Innocenzi A, Tedesco FS, Moreno-Fortuny A, Ugarte G, Lampugnanui MG, Messina G and Cossu G. 2013. Dll4 and PDGF-BB convert committed skeletal myoblasts to pericytes without erasing their myogenic memory. Developmental Cell 24, 586-599. PMID: 23477786

Michael Duchen

403. Sajic M, Mastrolia V, Lee CY, Trigo D, Sadeghian M, Mosley AJ, Gregson NA, Duchen MR, Smith KJ. Impulse conduction increases mitochondrial transport in adult mammalian peripheral nerves in vivo. PLoS Biol. 2013 Dec;11(12):e1001754. Epub 2013 Dec 31. PMID: 24391474;

404. Corona JC, de Souza SC, Duchen MR. PPARγ activation rescues mitochondrial function from inhibition of complex I and loss of PINK1. Exp Neurol. 2014 Mar;253:16-27. Epub 2013 Dec 26. PMID: 24374061.

405. Logan CV, Szabadkai G, Sharpe JA, Parry DA, Torelli S, Childs AM, Kriek M, Phadke R, Johnson CA, Roberts NY, Bonthron DT, Pysden KA, Whyte T, Munteanu I, Foley AR, Wheway G, Szymanska K, Natarajan S, Abdelhamed ZA, Morgan JE, Roper H, Santen GW, Niks EH, van der Pol WL, Lindhout D, Raffaello A, De Stefani D, den Dunnen JT, Sun Y, Ginjaar I, Sewry CA, Hurles M, Rizzuto R; UK10K Consortium, Duchen MR, Muntoni F, Sheridan E. Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium

40 | P a g e signaling. Nat Genet. 2014 Feb;46(2):188-93. Epub 2013 Dec 15. PMID: 24336167.

406. Kotiadis VN, Duchen MR, Osellame LD. Mitochondrial quality control and communications with the nucleus are important in maintaining mitochondrial function and cell health. Biochim Biophys Acta. 2014 Apr;1840(4):1254-65. Epub 2013 Nov 6. Review. PMID: 24211250

407. Osellame LD, Duchen MR. Quality control gone wrong: mitochondria, lysosomal storage disorders and neurodegeneration. Br J Pharmacol. 2014 Apr;171(8):1958-72. Review. PMID: 24116849

408. Chouchani ET, Pell VR, Gaude E, Aksentijević D, Sundier SY, Robb EL, Logan A, Nadtochiy SM, Ord EN, Smith AC, Eyassu F, Shirley R, Hu CH, Dare AJ, James AM, Rogatti S, Hartley RC, Eaton S, Costa AS, Brookes PS, Davidson SM, Duchen MR, Saeb-Parsy K, Shattock MJ, Robinson AJ, Work LM, Frezza C, Krieg T, Murphy MP. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014 Nov 20;515(7527):431-5. Epub 2014 Nov 5. PMID: 25383517

409. Corona JC, Duchen MR. Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets? J Bioenerg Biomembr. 2015 Apr;47(1-2):89-99. Epub 2014 Sep 13. Review. PMID: 25216534 Blacker TS, Mann ZF, Gale JE, Ziegler M, Bain AJ, Szabadkai G, Duchen MR. Separating NADH and NADPH fluorescence in live cells and tissues using FLIM. Nat Commun. 2014 May 29;5:3936. PMID: 24874098;

410. Ivanes F, Faccenda D, Gatliff J, Ahmed AA, Cocco S, Cheng CH, Allan E, Russell C, Duchen MR, Campanella M. The compound BTB06584 is an IF1 -dependent selective inhibitor of the mitochondrial F1 Fo-ATPase. Br J Pharmacol. 2014 Sep;171(18):4193-206. Epub 2014 Jul 1. PMID:24641180

411. Davidson SM, Foote K, Kunuthur S, Gosain R, Tan N, Tyser R, Zhao YJ, Graeff R, Ganesan A, Duchen MR, Patel S, Yellon DM. Inhibition of NAADP signalling on reperfusion protects the heart by preventing lethal calcium oscillations via two-pore channel 1 and opening of the mitochondrial permeability transition pore. Cardiovasc Res. 2015 Dec 1;108(3):357-66. Epub 2015 Sep 22. PMID: 26395965

412. Bhosale G, Sharpe JA, Sundier SY, Duchen MR. Calcium signaling as a mediator of cell energy demand and a trigger to cell death. Ann N Y Acad Sci. 2015 Sep;1350:107- 16.. Review. PMID: 26375864

413. Guedes-Dias P, de Proença J, Soares TR, Leitão-Rocha A, Pinho BR, Duchen MR, Oliveira JM. HDAC6 inhibition induces mitochondrial fusion, autophagic flux and reduces diffuse mutant huntingtin in striatal neurons. Biochim Biophys Acta. 2015 Nov;1852(11):2484-93. Epub 2015 Aug 21. PMID: 26300485.

414. Nickel AG, von Hardenberg A, Hohl M, Löffler JR, Kohlhaas M, Becker J, Reil JC, Kazakov A, Bonnekoh J, Stadelmaier M, Puhl SL, Wagner M, Bogeski I, Cortassa S, Kappl R, Pasieka B, Lafontaine M, Lancaster CR, Blacker TS, Hall AR, Duchen MR, Kästner L, Lipp P, Zeller T, Müller C, Knopp A, Laufs U, Böhm M, Hoth M, Maack C. Reversal of Mitochondrial Transhydrogenase Causes Oxidative Stress in Heart Failure. Cell Metab. 2015 Sep 1;22(3):472-84. Epub 2015 Aug 6. PMID: 26256392.

415. Shahni R, Cale CM, Anderson G, Osellame LD, Hambleton S, Jacques TS, Wedatilake Y, Taanman JW, Chan E, Qasim W, Plagnol V, Chalasani A, Duchen MR,

41 | P a g e Gilmour KC, Rahman S. Signal transducer and activator of transcription 2 deficiency is a novel disorder of mitochondrial fission. Brain. 2015 Oct;138(Pt 10):2834-46. Epub 2015 Jun 29. PMID: 26122121.

416. Levine AP, Duchen MR, de Villiers S, Rich PR, Segal AW. Alkalinity of neutrophil phagocytic vacuoles is modulated by HVCN1 and has consequences for myeloperoxidase activity. PLoS One. 2015 Apr 17;10(4):e0125906. eCollection 2015. PMID: 25885273

417. Llorente-Folch I, Rueda CB, Pardo B, Szabadkai G, Duchen MR, Satrustegui J. The regulation of neuronal mitochondrial metabolism by calcium. J Physiol. 2015 Aug 15;593(16):3447-62. Review. PMID: 25809592

418. Blacker TS, Duchen MR. Investigating mitochondrial redox state using NADH and NADPH autofluorescence. Free Radic Biol Med. 2016 Aug 9. [Epub ahead of print] PMID: 27519271.

419. Bolaños JP, Cadenas E, Duchen MR, Hampton MB, Mann GE, Murphy MP. Introduction to Special Issue on Mitochondrial Redox Signaling in Health and Disease. Free Radic Biol Med. 2016 Aug 5. [Epub ahead of print] PMID: 27502830.

420. Corona JC, Duchen MR. PPARγ as a therapeutic target to rescue mitochondrial function in neurological disease. Free Radic Biol Med. 2016 Jun 25. [Epub ahead ofprint] PMID: 27352979. McKenzie M, Duchen MR. Impaired Cellular Bioenergetics Causes Mitochondrial Calcium Handling Defects in MT-ND5 Mutant Cybrids. PLoS One. 2016 Apr 25;11(4):e0154371.. eCollection 2016. PMID: 27110715

421. Hawkins KE, Joy S, Delhove JM, Kotiadis VN, Fernandez E, Fitzpatrick LM, Whiteford JR, King PJ, Bolanos JP, Duchen MR, Waddington SN, McKay TR. NRF2 Orchestrates the Metabolic Shift during Induced Pluripotent Stem Cell Reprogramming. Cell Rep. 2016 Mar 1;14(8):1883-91. Epub 2016 Feb 18. PMID: 26904936

Elizabeth Fisher

422. Fratta, P., Charnock, J., Collins, T., Devoy, A., Howard, R., Malaspina, A., Orrell, R., Sidle, K., Clarke, J., Shoai, M., Lu, C-H., Hardy, J., Plagnol, V., Fisher, E.M.C. (2013) Profilin E117G is a moderate risk factor for amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry, 2013 Dec 5. PMID: 24309268.

423. Fratta, P., Hanna, M.G., Fisher, E.M.C., Sidle, K. (2013) An unusual presentation for SOD1-ALS: isolated facial diplegia. Muscle and Nerve. 48: 994-995 PMID:23873540.

424. Thorne, T., Fratta, P., Hanna, M.G., Cortese, A., Plagnol, V., Fisher, E.M.C., Stumpf, M.P.H. (2013) Graphical modelling of molecular networks underlying sporadic inclusion body myositis. Molecular Biosystems 9: 1736-1742. PMID:23595110.

425. Fratta, P., Malik, B., Gray, A., La Spada, A., Hanna, M.G., Fisher, E.M.C., Greensmith, L. (2013) FUS is not dysregulated by the spinal bulbar muscular atrophy androgen receptor polyglutamine repeat expansion. Neurobiol Aging 34: 1516e17-1516e19. PMID:23062703.

426. Schiavo, G., Greensmith, L., Hafezparast, M., Fisher, E.M.C. (2013). Cytoplasmic Dynein Heavy Chain: the servant of many masters. Trends in Neurosciences 36, 641-651. PMID: 24035135.

42 | P a g e 427. McGoldrick, P., Joyce, P.I., Fisher, E.M.C., Greensmith, L. (2013). Rodent models of amyotrophic lateral sclerosis. Biochim Biophys Acta 1832: 1421-1436. PMID: 23524377.

428. Saccon, R., Bunton-Stasyshyn, R., Fisher, E.M.C.*, Fratta, P. (2013). Is SOD1 loss of function involved in amyotrophic lateral sclerosis? Brain, 136: 2342-2358. PMID: 23687121.

429. Bunton-Stasyshyn, R.K.A., Saccon, R.A., Fratta, P., Fisher, E.M.C. (2014) SOD1 function and its implications for ALS pathology: New and renascent themes. The Neuroscientist, 1-11. PMID: 25492944.

430. Mizielinska, S., Grönke, Niccoli, T., Ridler, C.E., Clayton, E.L., Devoy, A., Moens, T., Norona, F.E., Woollacott, I.O.C., Pietrzyk, J., Cleverley, K., Nicoll, A.J., Pickering-Brown, S., Dols, J., Cabecinha, M., Hendrich, O., Fratta, P., Fisher, E.M.C., Partridge, L., Isaacs, A.M. (2014) C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine- rich proteins. Science 345: 1192-1194 PMID: 25103406.

431. Fratta, P., Nirmalananthan, N., Masset, L., Skorupinska, I., Collins, T., Cortese, A., Pemble, S., Malaspina, A., Fisher, E.M.C., Greensmith, L., Hanna, M. (2014) Correlation of clinical and molecular features in spinal bulbar muscular atrophy. Neurology 82: 1-8 PMID: 24814851.

432. Cortese, A., Plagnol, V., Brady, S., Simone, R., Lashley, T., Acevedo-Arozena, A., de Silva, R., Greensmith, L., Holton, J., Hanna, M.G., Fisher, E.M.C., Fratta, P. (2014) Widespread RNA metabolism is impaired in sporadic inclusion body myositis TDP43- proteinopathy. Neurobiol Ageing 35: 1491-1498 PMID: 24462217.

433. Da Ma, Cardoso, M.J., Modat, M., Powell, N., Wells, J., Holmes, H., Wiseman, F., Tybulewicz, V.L.J., Fisher, E.M.C., Lythgoe, M. F., Ourselin, S.O. (2014) Automatic Structural Parcellation of Mouse Brain MRI using Multi-Atlas Label Fusion. PLOS ONE 9(1): e86576. PMID: 24475148.

434. Garrett, C.A., Barri, M., Kuta, A., Soura, V., Deng, W., Fisher, E.M.C., Schiavo, G., Hafezparast, M. (2014) DYNC1H1 mutation alters transport kinetics and ERK1/2-cFos signalling in a mouse model of distal spinal muscular atrophy. Brain 137: 1883-1893 PMID: 24755273.

435. Ricketts, T., McGoldrick, P., Fratta, P., Kent, R., Phatak, V., Brandner, S., Greensmith L., Acevedo-Arozena, A., Fisher E.M.C. (2014) A nonsense mutation in mouse Tardbp affects TDP43 alternative splicing activity and causes limb-clasping and body tone defects. PLoS ONE 9(1): e85962. PMID: 24465814.

436. Fratta, P., Collins, T., Pemble, S., Nethisinghe, S., Devoy, A., Giunti, P., Sweeney, M.G., Hanna, M.G., Fisher, E.M.C. (2014) Sequencing analysis of the SBMA CAG expansion reveals absence of repeat interruptions. Neurobiol Ageing. 443.e1-443.e3. PMID: 24041967.

437. Joyce, P.I., Fratta, P., Landman, A., McGoldrick, P., Wackerhage, H., Groves, M., Busam, B.S., Galino, J., Corrochano, S., Beskina, O.A., Esapa, C., Ryder, E., Carter, S., Stewart, M., Codner, G., Hilton, H., Teboul, L., Lionikas, A., Estabel, J., Ramirez-Solis, R., White, J.K., Tucker, J., Brandner, S., Plagnol V., Bennett, L.H., Abramov, A.Y., Greensmith, L., Fisher, E.M.C.*, Acevedo-Arozena, A.* (2015) Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration. Hum Molec Genet. 25: 291-307. PMID: 26604141

438. Joyce, P.I., McGoldrick, P., Saccon, R. A., Weber, W., Fratta, P., West, S. J., Zhu, N., Carter, S., Phatak, V., Stewart, M., Simon, M., Kumar, S., Heise, I., Bros-Facer, V., Dick, J., Luong, T., Nolan, P.M., Meyer, T., Brandner, S., Bennett, D.L.H., Ozdinler, P.H.,

43 | P a g e Greensmith, L., Fisher, E.M.C.*, Acevedo-Arozena, A. (2015) A SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity. Hum. Molec. Genet. 24: 1883-1897. PMID: 25468678. *corresponding author.

439. Fratta P, Polke JM, Newcombe J, Mizielinska S, Lashley T, Poulter M, Beck J, Preza E, Devoy A, Sidle K, Howard R, Malaspina A, Orrell RW, Clarke J, Lu CH, Mok K, Collins T, Shoaii M, Nanji T, Wray S, Adamson G, Pittman A, Renton AE, Traynor BJ, Sweeney MG, Revesz T, Houlden H, Mead S, Isaacs AM, Fisher EM.C.(2015) Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion. Neurobiol Aging. 36: 546.e1–546.e7. PMID: 25179228.

Linda Greensmith

440. B Malik, N Nirmalananthan, A Gray, AR La Spada, MG Hanna & L Greensmith (2013) Co-induction of the heat shock response ameliorates disease in a mouse model of human Spinal Bulbar Muscular Atrophy: implications for therapy Brain 136 (Pt 3):926-43. PMID:23393146

441. P Fratta, B Malik, A Gray, A La Spada, MG Hanna, EM Fisher and L Greensmith (2013) FUS is not dysregulated by the SBMA Androgen Receptor polyglutamine repeat expansion Neurobiology of Aging 34(5):1516. e17-9 PMID:23062703

442. JC Mitchell, P McGoldrick, CA Vance, T Hortobagyi, J Sreedharan, B Rogelj, EL Tudor, N Smith, C Klasen, CC Miller, JD Cooper, L Greensmith & CE Shaw (2013) Overexpression of human wild-type FUS causes progressive motor neuron degeneration in an age and dose- dependent fashion Acta Neuropathologia 125(2):273-88 PMID:22961620

443 EC Oates*, AM Rossor*, M Hafezparast, M Gonzalez, F Speziani, DG MacArthur, M Lek, E Cottenie, M Scoto, AR Foley, M Hurles, H Houlden, L Greensmith, M Auer- Grumbach, TR Pieber, TM Strom, R Schule, DN Herrmann, JE Sowden, G Acsadi, MP Menezes, NF Clarke, S Züchner, UK10K, F Muntoni, KN North†, MM Reilly†. (2013) Mutations in BICD2 cause Dominant Congenital Spinal Muscular Atrophy (DCSMA) and Hereditary Spastic Paraplegia (HSP). American Journal of Human Genetics 92, 965–973 PMID: 23664120

444. McGoldrick P, Joyce PI, Fisher EM & Greensmith L (2013) Rodent models of amyotrophic lateral sclerosis. Biochim Biophys Acta 1832 (9):1421-36 PMID: 23524377

445. G Schiavo, L Greensmith, M Hafezparast & E.M.C. Fisher (2013) Cytoplasmic dynein heavy chain: the servant of many masters. Trends Neurosci, 36 (11): 641-651. PMID:24035135

446. SS Novoselov*, W J. Mustill*, A L Gray, J R Dick, N Kanuga, B Kalmar, L Greensmith & M E. Cheetham (2013) Molecular chaperone mediated late-stage neuroprotection in the SOD1G93A mouse model of amyotrophic lateral sclerosis. PLOS One 8 (8): e73944. PMID: 24023695

447. C J Sumner, C d’Ydewalle, J Wooley, KA Fawcett, D Hernandez, AR Gardiner, B Kalmar, R H Baloh, M Gonzalez, S Züchner, HC Stanescu, R Kleta, A Mankodi, DR Cornblath, KB Boylan, MM Reilly, L Greensmith, AB Singleton, MB Harms, AM Rossor and H Houlden (2013) Dominant mutation of FBXO38 causes distal spinal muscular atrophy with calf predominance. American Journal of Human Genetics 93 (5): 976-983. PMID: 24207122

44 | P a g e 448. B Kalmar*, C-Hua Lu* and L Greensmith (2014) The role of heat shock proteins in Amyotrophic Lateral Sclerosis: the therapeutic potential of Arimoclomol. Pharmacology and Therapeutics Reviews 141 (1): 40-54 PMID: 23978556

449. *T Ricketts*, P McGoldrick*, P Fratta3, R Kent, V Phatak, S Brandner, L Greensmith, A Acevedo-Arozena and E.M.C. Fisher, (2014) A nonsense mutation in mouse Tardbp causes a loss of TDP43 alternative splicing activity in the absence of motor dysfunction. PLOS One 9 (1):e85962 PMID: 24465814

450. *A Cortese, V Plagnol, S Brady, R Simone, T Lashley, A Acevedo-Arozena, R de Silva, L Greensmith, J Holton, M Hanna, E Fisher and P Fratta. (2014) Widespread RNA metabolism impairment in sporadic inclusion body myositis TDP43-proteinopathy Neurobiology of Aging 35 (6):1491-8 PMID:24462217

451. *P Fratta, N Nirmalananthan, L Masset, I Skorupinska, T Collins, A Cortese, S Pemble, A Malaspina, E Fisher, L Greensmith and M Hanna (2014) Correlation of clinical and molecular features in spinal bulbar muscular atrophy. Neurology 82(23):2077-84. PMID:24814851

452. JB Bryson, CB Machado, M Crossley, D Stevenson, V Bros-Facer, J Burrone , L Greensmith# and I Lieberam# (2014) Optical-control of muscle function by transplantation of stem cell-derived motoneurons in mice. Science 344(6179):94-7 PMID:24700859

453. V Bros-Facer, D Krull, A Taylor, JRT Dick, SA Bates, MS Cleveland, RK Prinjha and L Greensmith (2014) Treatment with an antibody directed against Nogo-A delays disease progression in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis. Human Molecular Genetics 23(16):4187-200. PMID:24667415

454. *K Montague, B Malik, AL Gray, A R La Spada, MG Hanna, G Szabadkai & L Greensmith (2014) Endoplasmic reticulum stress in Spinal and Bulbar Muscular Atrophy- a potential target for therapy. Brain 137(Pt 7):1894-906. PMID: 24898351

456. LK Petchey, CA Risebro, JM Vieira, T Roberts, JB Bryson, L Greensmith, MF Lythgoe & PR Riley (2014) Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fibre- type conversion and dilated cardiomyopathy. PNAS 111(26):9515-20 PMID: 24938781

457. J Carroll, TK Page, SC Chiang, B Kalmar, D Bode, L Greensmith, PJ Mckinnon , JR Thorpe, M Hafezparast & SF El-Khamisy (2015) Expression of a pathogenic mutation of SOD1 sensitizes aprataxin-deficient cells and mice to oxidative stress and triggers hallmarks of premature ageing. Hum Mol Genet. 24(3): 828-40. PMID: 25274775

458. M Mielcarek, M Toczek, C Smeets, SA Franklin, MK Bondulich, N Jolinnon,Muller, M Ahmed, JRT Dick, I Piotrowska, L Greensmith, RT Smolenski and GP Bates (2015) HDAC4-myogenin axis as an important marker of HD-related skeletal muscles atrophy. PLOS Genetics 11(3). PMID: 25748626

459. C-H Lu, C Macdonald-Wallis, E Gray, N Pearce, A Petzold, N Norgren, G Giovannoni, P Fratta, K Sidle, M Fish, R Orrell, R Howard, K Talbot, L Greensmith, J Kuhle, MR Turner, A Malaspina (2015) Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84(22):2247-57. PMID: 26346831

460. M Pennuto, L Greensmith, PF Pradat, Sorarù G; European SBMA Consortium(2015). 210th ENMC International Workshop: Research and clinical management of patients with

45 | P a g e spinal and bulbar muscular atrophy, 27-29 March, 2015, Naarden, The Netherlands. Neuromuscular Disorders 25 (10) 802-812. PMID: 26206601

461. NR Martin, SL Passey, DJ Player, V Mudera, K Baar, L Greensmith and M Lewis M (2015). Neuromuscular junction formation in tissue engineered skeletal muscle augments contractile function and improves cytoskeletal organisation. Tissue Eng Part A. 21(19- 20):2595-604. PMID: 26166548

462. R Rusmini, V Crippa, R Cristofani, C Rinaldi, S Carra, B Malik, Greensmith L*, Poletti A* (2015). The role of the protein quality control system in SBMA. J Mol Neurosci 58, 348- 364. C Rinaldi, B Malik and L Greensmith L (2015) Targeted molecular therapies for SBMA. J Mol Neurosci 58, 335-342. PMID: 26572535

463. KL Gibbs, L Greensmith & G Schiavo (2015) Regulation of Axonal Transport by Protein Kinases. Trends Biochem Sci. 40(10):597-610. PMID: 26410600

464. Joyce PI, Mcgoldrick P, Saccon RA, Weber W, Fratta P, West SJ, Zhu N, Carter S, Phatak V, Stewart M, Simon M, Kumar S, Heise I, Bros-Facer V, Dick J, Corrochano S, Stanford MJ, Luong TV, Nolan PM, Meyer T, Brandner S, Bennett DL, Ozdinler PH, Greensmith L, Fisher EM, Acevedo-Arozena A. A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity. Hum Mol Genet. 2015 Apr 1;24(7):1883-97. PMID: 25468678

465. Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, Giovannoni G, Fratta P, Sidle K, Fish M, Orrell R, Howard R, Talbot K, Greensmith L, Kuhle J, Turner MR, Malaspina A. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology. 2015 Jun 2;84(22):2247-57. PMID: 25934855

466. Martin NR, Passey SL, Player DJ, Mudera V, Baar K, Greensmith L, Lewis M.Neuromuscular junction formation in tissue engineered skeletal muscle augments contractile function and improves cytoskeletal organisation. Tissue Eng Part A. 2015 Jul 13. [Epub ahead of print] PMID: 26166548.

467. C-H Lu, K Allen, F Oei, E Leoni, J Kuhle, T Tree, P Fratta, N Sharma, K Sidle, R Howard, R Orrell, M Fish, L Greensmith, N Pearce, V Gallo and A Malaspina (2016) Systemic inflammatory response and neuromuscular involvement in Amyotrophic Lateral Sclerosis Neurology, Neuroimmmunology and Neuroinflammation 2016 Jun 1;3(4):e244. eCollection 2016. PMID: 2730

468. A Smith A, S Passey, N Martin, D Player, V Mudera, L Greensmith L and M Lewis. Creating Interactions Between Tissue-Engineered Skeletal Muscle and the Peripheral Nervous System Cells, Tissues, Organs In Press

469. P Joyce, P Fratta, A Landman#, P McGoldrick#, H Wackerhage, M Groves, B Shiva Busam, J Galino, S Corrochano, O Beskina, C Esapa, E Ryder, S Carter, M Stewart, G Codner, H Hilton, L Teboul, A Lionikas, J Estabel, A Lionikas, JK White, J Tucker, S Brandner, V Plagnol, DLH Bennet, A Abramov, L Greensmith*, E Fisher* & A Acevedo Arozena* (2016) Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration in mice. Hum Mol Genetics 25(2):291-307. PMID: 26604141

470. KL Gibbs, B Kalmar, JN Sleigh, L Greensmith and G Schiavo (2016). In vivo imaging of axonal transport in murine motor and sensory neurons. J Neurosci Methods 257:26-33. PMID: 26424507

46 | P a g e 471. JB Bryson, C Barcellos Machado, I Lieberam and L Greensmith (2016). Restoring motor function using optogenetics and neural replacement. Current Opinion in Biotechnology 40, 75-81. PMID: 27016703

472. M Ahmed, P Machado, A Miller, L Herbelin, J He, J Noel, Y Wang, AL McVey, MPasnoor, P Gallagher, J Statland, C-H Lu, B Kalmar, S Brady, H Sethi, G Samandouras, M Parton, J Holton, MG Hanna, RJ Barohn, MM Dimachkie & L Greensmith (2016) Targeting protein homeostasis as a novel therapeutic approach in Sporadic Inclusion Body Myositis. Science Translational Medicine 8, 331ra41 PMID: 27009270

473. AM Rossor, C-H Liu, A Petzold, A Malaspina, M Laura, L Greensmith, MM Reilly (2016) Plasma neurofilament heavy chain is not a useful biomarker in Charcot-Marie-Tooth Disease. Muscle and Nerve 53, 972-975. PMID: 27015106

Henry Houlden

474. Sumner CJ, d'Ydewalle C, Wooley J, Fawcett KA, Hernandez D, Gardiner AR,Kalmar B, Baloh RH, Gonzalez M, Zachner S, Stanescu HC, Kleta R, Mankodi A,Cornblath DR, Boylan KB, Reilly MM, Greensmith L, Singleton AB, Harms MB, Rossor AM, Houlden H.A dominant mutation in FBXO38 causes distal spinal muscular atrophy with calf predominance. Am J Hum Genet. 2013 Nov 7;93(5):976-83. PMID: 24207122

475. Nalini A, Pandraud A, Mok K, Houlden H. Madras motor neuron disease (MMND) isdistinct from the riboflavin transporter genetic defects that cause Brown-Vialetto-Van Laere syndrome. J Neurol Sci. 2013 Nov 15;334(1-2):119-22.PMID: 24139842

476. Rossor AM, Polke JM, Houlden H, Reilly MM. Clinical implications of genetic advances in Charcot-Marie-Tooth disease. Nat Rev Neurol. 2013 Oct;9(10):562-71. PMID: 24018473

477. Bettencourt C, Morris HR, Singleton AB, Hardy J, Houlden H. Exome sequencing expands the mutational spectrum of SPG8 in a family with spasticity responsive toL-DOPA treatment. J Neurol. 2013 Sep;260(9):2414-6. PMID: 23881105

478. Kruer MC, Jepperson T, Dutta S, Steiner RD, Cottenie E, Sanford L, Merkens M,Russman BS, Blasco PA, Fan G, Pollock J, Green S, Woltjer RL, Mooney C,Kretzschmar D, Paisán-Ruiz C, Houlden H. Mutations in γ adducin are associated with inherited cerebral palsy. Ann Neurol. 2013 Dec;74(6):805-14. PMID: 23836506

479. Pitceathly RD, Rahman S, Wedatilake Y, Polke JM, Cirak S, Foley AR, Sailer A,Hurles ME, Stalker J, Hargreaves I, Woodward CE, Sweeney MG, Muntoni F, Houlden H, Taanman JW, Hanna MG; UK10K Consortium. NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease. Cell Rep. 2013 Jun 27;3(6):1795-805. PMID: 23746447

480. Gonzalez M, McLaughlin H, Houlden H, Guo M, Yo-Tsen L, Hadjivassilious M, Speziani F, Yang XL, Antonellis A, Reilly MM, Zachner S; Inherited Neuropathy Consortium. Exome sequencing identifies a significant variant in methionyl-tRNAsynthetase (MARS) in a family with late-onset CMT2. J Neurol Neurosurg Psychiatry. 2013 Nov; 84(11):1247-9. PMID: 23729695

481. Rossor AM, Hafezparast M, Gonzalez M, Speziani F, MacArthur DG, Lek M, Cottenie E, Scoto M, Foley AR, Hurles M, Houlden H, Greensmith L, Auer-Grumbach M, Pieber TR, Strom TM, Schule R, Herrmann DN, Sowden JE, Acsadi G,Menezes MP, Clarke NF, Züchner S; UK10K, Muntoni F, North KN, Reilly MM. Mutations in BICD2 cause dominant

47 | P a g e congenital spinal muscular atrophy andhereditary spastic paraplegia. Am J Hum Genet. 2013 Jun 6;92(6):965-73. PMID: 23664120

482. Murphy SM, Ernst D, Wei Y, Laura M, Liu YT, Polke J, Blake J, Winer J, Houlden H, Hornemann T, Reilly MM. Hereditary sensory and autonomic neuropathytype 1 (HSANI) caused by a novel mutation in SPTLC2. Neurology. 2013 Jun 4;80(23):2106-11. PMID: 23658386

483. Bartolome F, Wu HC, Burchell VS, Preza E, Wray S, Mahoney CJ, Fox NC, Calvo A, Canosa A, Moglia C, Mandrioli J, Chiò A, Orrell RW, Houlden H, Hardy J, Abramov AY, Plun-Favreau H. Pathogenic VCP mutations induce mitochondrialuncoupling and reduced ATP levels. Neuron. 2013 Apr 10;78(1):57-64. PMID: 23498975

484. Cottenie E, Menezes MP, Rossor AM, Morrow JM, Yousry TA, Dick DJ, Anderson JR, Jaunmuktane Z, Brandner S, Blake JC, Houlden H, Reilly MM. Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy. Neuromuscul Disord. 2013 May; 23(5):399-403. PMID: 23489662.

485. Houlden H. Defective N-linked protein glycosylation pathway in congenital myasthenic syndromes. Brain. 2013 Mar;136(Pt 3):692-5. PMID: 23436500

486. Hersheson J, Mencacci NE, Davis M, MacDonald N, Trabzuni D, Ryten M, Pittman A, Paudel R, Kara E, Fawcett K, Plagnol V, Bhatia KP, Medlar AJ, Stanescu HC,Hardy J, Kleta R, Wood NW, Houlden H. Mutations in the autoregulatory domain of β-tubulin 4a cause hereditary dystonia. Ann Neurol. 2013 Apr;73(4):546-53. PMID: 23424103

487. Silveira-Moriyama L, Gardiner AR, Meyer E, King MD, Smith M, Rakshi K, Parker A, Mallick AA, Brown R, Vassallo G, Jardine PE, Guerreiro MM, Lees AJ, Houlden H, Kurian MA. Clinical features of childhood-onset paroxysmal kinesigenic dyskinesia with PRRT2 gene mutations. Dev Med Child Neurol. 2013 Apr;55(4):327-34. PMID: 23363396

488. Hammer MB, Eleuch-Fayache G, Schottlaender LV, Nehdi H, Gibbs JR, Arepalli SK, Chong SB, Hernandez DG, Sailer A, Liu G, Mistry PK, Cai H, Shrader G, Sassi C, Bouhlal Y, Houlden H, Hentati F, Amouri R, Singleton AB. Mutations in GBA2 cause autosomal- recessive cerebellar ataxia with spasticity. Am J Hum Genet. 2013 Feb 7;92(2):245-51. PMID: 23332917

489. Cregg R, Laguda B, Werdehausen R, Cox JJ, Linley JE, Ramirez JD, Bodi I,Markiewicz M, Howell KJ, Chen YC, Agnew K, Houlden H, Lunn MP, Bennett DL, Wood JN, Kinali M. Novel mutations mapping to the fourth sodium channel domain ofNav1.7 result in variable clinical manifestations of primary erythromelalgia.Neuromolecular Med. 2013 Jun;15(2):265- 78. PMID: 23292638

490. Fawcett K, Mehrabian M, Liu YT, Hamed S, Elahi E, Revesz T, Koutsis G,Herscheson J, Schottlaender L, Wardle M, Morrison PJ, Morris HR, Giunti P, Wood N, Houlden H. The frequency of spinocerebellar ataxia type 23 in a UK population.J Neurol. 2013 Mar;260(3):856-9. PMID: 23108490

491. Tucci A, Kara E, Schossig A, Wolf NI, Plagnol V, Fawcett K, Paisán-Ruiz C,Moore M, Hernandez D, Musumeci S, Tennison M, Hennekam R, Palmeri S, Malandrini A, Raskin S, Donnai D, Hennig C, Tzschach A, Hordijk R, Bast T, Wimmer K, Lo CN, Shorvon S, Mefford H, Eichler EE, Hall R, Hayes I, Hardy J, Singleton A, Zschocke J, Houlden H. Kohlschütter- Tönz syndrome: mutations in ROGDI and evidence ofgenetic heterogeneity. Hum Mutat. 2013 Feb;34(2):296-300. PMID: 23086778

48 | P a g e 492. Thomas AC, Williams H, Setó-Salvia N, Bacchelli C, Jenkins D, O'Sullivan M,Mengrelis K, Ishida M, Ocaka L, Chanudet E, James C, Lescai F, Anderson G,Morrogh D, Ryten M, Duncan AJ, Pai YJ, Saraiva JM, Ramos F, Farren B, Saunders D,Vernay B, Gissen P, Straatmaan-Iwanowska A, Baas F, Wood NW, Hersheson J, Houlden H, Hurst J, Scott R, Bitner-Glindzicz M, Moore GE, Sousa SB, Stanier P. Mutationsin SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome. Am J Hum Genet. 2014 Nov 6;95(5):611-21. PMID: 25439728

493. Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A,Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P,Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I,Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M,Kabzińska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H.Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Am J Hum Genet. 2014 Nov 6;95(5):590-601. PMID: 25439726

494. Machado PM, Ahmed M, Brady S, Gang Q, Healy E, Morrow JM, Wallace AC, Dewar L, Ramdharry G, Parton M, Holton JL, Houlden H, Greensmith L, Hanna MG. Ongoing developments in sporadic inclusion body myositis. Curr Rheumatol Rep. 2014 Dec;16(12):477. PMID: 25399751

495. Hersheson J, Burke D, Clayton R, Anderson G, Jacques TS, Mills P, Wood NW, Gissen P, Clayton P, Fearnley J, Mole SE, Houlden H. Cathepsin D deficiencycauses juvenile- onset ataxia and distinctive muscle pathology. Neurology. 2014 Nov 11;83(20):1873-5. PMID: 25298308

496. Horga A, Pitceathly RD, Blake JC, Woodward CE, Zapater P, Fratter C,Mudanohwo EE, Plant GT, Houlden H, Sweeney MG, Hanna MG, Reilly MM. Peripheralneuropathy predicts nuclear gene defect in patients with mitochondria lophthalmoplegia. Brain. 2014 Dec;137(Pt 12):3200-12: PMID: 25281868

497. Manole A, Fratta P, Houlden H. Recent advances in bulbar syndromes: genetic causes and disease mechanisms. Curr Opin Neurol. 2014 Oct;27(5):506-14. PMID: 25159929

498. Liu YT, Laura M, Hersheson J, Horga A, Jaunmuktane Z, Brandner S, Pittman A, Hughes D, Polke JM, Sweeney MG, Proukakis C, Janssen JC, Auer-Grumbach M, Zuchner S, Shields KG, Reilly MM, Houlden H. Extended phenotypic spectrum of KIF5A mutations: From spastic paraplegia to axonal neuropathy. Neurology. 2014 Aug12;83(7):612-9. PMID: 25008398

499. Gang Q, Bettencourt C, Machado P, Hanna MG, Houlden H. Sporadic inclusion body myositis: the genetic contributions to the pathogenesis. Orphanet J RareDis. 2014 Jun 19;9:88. PMID:24948216

500. Nowak VA, Bremner F, Massey L, Wokke B, Moosavi R, Kara E, Houlden H. Kjellinsyndrome: hereditary spastic paraplegia with pathognomonic macular appearance.Pract Neurol. 2014 Aug;14(4):278-9. PMID: 24924740

501. Bettencourt C, Ryten M, Forabosco P, Schorge S, Hersheson J, Hardy J, Houlden H; United Kingdom Brain Expression Consortium. Insights from cerebellartranscriptomic analysis into the pathogenesis of ataxia. JAMA Neurol. 2014 Jul1;71(7):831-9. PMID: 24862029

49 | P a g e 502. Boizot A, Talmat-Amar Y, Morrogh D, Kuntz NL, Halbert C, Chabrol B, Houlden H, Stojkovic T, Schulman BA, Rautenstrauss B, Bomont P. The instability of the BTB-KELCH protein Gigaxonin causes Giant Axonal Neuropathy and constitutes a new penetrant and specific diagnostic test. Acta Neuropathol Commun. 2014 Apr24;2:47. PMID: 24758703

503. Bertini E, Houlden H. Defects of RNA metabolism in the pathogenesis of spinal muscular atrophy. Neurology. 2014 Apr 15;82(15):1298-9. PMID: 24647031

504. Wiethoff S, Xiromerisiou G, Bettencourt C, Kioumi A, Tsiptsios I, Tychalas A,Evaggelia M, George K, Makris V, Hardy J, Houlden H. Novel single base-pairdeletion in exon 1 of XK gene leading to McLeod syndrome with chorea, musclewasting, peripheral neuropathy, acanthocytosis and haemolysis. J Neurol Sci. 2014 Apr 15;339(1-2):220-2. PMID: 24529944

505. Dale RC, Gardiner A, Branson JA, Houlden H. Benefit of carbamazepine in a patient with hemiplegic migraine associated with PRRT2 mutation. Dev Med ChildNeurol. 2014 Sep;56(9):910. PMID: 24506539

506. Kruer MC, Salih MA, Mooney C, Alzahrani J, Elmalik SA, Kabiraj MM, Khan AO,Paudel R, Houlden H, Azzedine H, Alkuraya F. C19orf12 mutation leads to apallido-pyramidal syndrome. Gene. 2014 Mar 10;537(2):352-6. PMID: 24361204

507. Foley AR, Menezes MP, Pandraud A, Gonzalez MA, Al-Odaib A, Abrams AJ, Sugano K, Yonezawa A, Manzur AY, Burns J, Hughes I, McCullagh BG, Jungbluth H, Lim MJ,Lin JP, Megarbane A, Urtizberea JA, Shah AH, Antony J, Webster R, Broomfield A,Ng J, Mathew AA, O'Byrne JJ, Forman E, Scoto M, Prasad M, O'Brien K, Olpin S,Oppenheim M, Hargreaves I, Land JM, Wang MX, Carpenter K, Horvath R, Straub V,Lek M, Gold W, Farrell MO, Brandner S, Phadke R, Matsubara K, McGarvey ML,Scherer SS, Baxter PS, King MD, Clayton P, Rahman S, Reilly MM, Ouvrier RA,Christodoulou J, Züchner S, Muntoni F, Houlden H. Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain. 2014 Jan;137(Pt 1):44-56. PMID:24253200

508. Liu YT, Hersheson J, Plagnol V, Fawcett K, Duberley KE, Preza E, HargreavesIP, Chalasani A, Laura M, Wood NW, Reilly MM, Houlden H. Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein:clinical, genetic and biochemical characterisation. J Neurol Neurosurg Psychiatry. 2014 May;85(5):493-8. PMID: 24218524

509. Koutsis G, Kladi A, Karadima G, Houlden H, Wood NW, Christodoulou K, Panas M.Friedreich's ataxia and other hereditary ataxias in Greece: an 18-year perspective. J Neurol Sci. 2014 Jan 15;336(1-2):87-92. PMID: 24209901

510. Tucci A, Liu YT, Preza E, Pitceathly RD, Chalasani A, Plagnol V, Land JM,Trabzuni D, Ryten M; UKBEC, Jaunmuktane Z, Reilly MM, Brandner S, Hargreaves I, Hardy J, Singleton AB, Abramov AY, Houlden H. Novel C12orf65 mutations inpatients with axonal neuropathy and optic atrophy. J Neurol Neurosurg Psychiatry. 2014 May;85(5):486-92. PMID: 24198383

511. Perumal MB, Kovac S, Shah A, Wood N, Houlden H, Eriksson S, Walker M.Hypersomnia with dilated pupils in adenosine monophosphate deaminase (AMPD)deficiency. J Sleep Res. 2014 Feb;23(1):118-20. PMID: 24033727

512. Beck J, Pittman A, Adamson G, Campbell T, Kenny J, Houlden H, Rohrer JD, deSilva R, Shoai M, Uphill J, Poulter M, Hardy J, Mummery CJ, Warren JD, Schott JM Fox NC,

50 | P a g e Rossor MN, Collinge J, Mead S. Validation of next-generation sequencingtechnologies in genetic diagnosis of dementia. Neurobiol Aging. 2014 Jan;35(1):261-5. PMID: 23998997

513. Mencacci NE, Erro R, Wiethoff S, Hersheson J, Ryten M, Balint B, Ganos C, Stamelou M, Quinn N, Houlden H, Wood NW, Bhatia KP ADCY5 mutations are another cause of benign hereditary chorea. Neurology. 2015 Jun 17. PMID: 26085604

514. Manole A, Houlden H. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Smith RJH, Stephens K. Riboflavin Transporter Deficiency Neuronopathy. editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. 2015 Jun 11. PMID: 26072523

515. Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzales MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. The p.Ser107Leu in BICD2 is a mutation 'hot spot' causing distal spinal muscular atrophy. Brain. 2015 Jun 10. pii: awv160. PMID: 26063657

516. Pappas SS, Darr K, Holley SM, Cepeda C, Mabrouk OS, Wong JT, LeWitt TM, Paudel R, Houlden H, Kennedy RT, Levine MS, Dauer WT. Forebrain deletion of the dystonia protein torsinA causes dystonic-like movements and loss of striatal cholinergic neurons. Elife. 2015 Jun 8;4:e08352. PMID: 26052670

517. Koutsis G, Lynch DS, Tucci A, Houlden H, Karadima G, Panas M. A novel ABCD1 mutation detected by next generation sequencing in presumed hereditary spastic paraplegia: A 30-year diagnostic delay caused by misleading biochemical findings. J Neurol Sci. 2015 May 29. [Epub ahead of print] PMID: 26049658

518. Wiethoff S, Arber C, Li A, Wray S, Houlden H, Patani R. Using human induced pluripotent stem cells (hiPSC) to model cerebellar disease: Hope and hype. J Neurogenet. 2015 May 19:1-25. [Epub ahead of print] PMID: 25985846

519. Khaleeli Z, Jaunmuktane Z, Beaufort N, Houlden H, Haffner C, Brandner S, Dichgans M, Werring D. A novel HTRA1 exon 2 mutation causes loss of protease activity in a Pakistani CARASIL patient. J Neurol. 2015 May;262(5):1369-72. doi: 10.1007/s00415-015-7769-5. Epub 2015 May 10. PMID: 25957642

520. Scalco RS, Gardiner AR, Pitceathly RD, Zanoteli E, Becker J, Holton JL, Houlden H, Jungbluth H, Quinlivan R. Rhabdomyolysis: a genetic perspective. Orphanet J Rare Dis. 2015 May 2;10(1):51. PMID: 25929793

521. Bettencourt C, Houlden H. Exome sequencing uncovers hidden pathways in familial and sporadic ALS. Nat Neurosci. 2015 Apr 28;18(5):611-3. PMID: 25919956

522. Federoff M, Schottlaender LV, Houlden H, Singleton A. Multiple system atrophy: the application of genetics in understanding etiology. Clin Auton Res. 2015 Feb;25(1):19-36. Epub 2015 Feb 17. PMID: 25687905

523. Horga A, Cottenie E, Tomaselli PJ, Rojas-García R, Salvado M, Villarreal-Pérez L, Gamez J, Márquez-Infante C, Houlden H, Reilly MM. Absence of HINT1 mutations in a UK and Spanish cohort of patients with inherited neuropathies. J Neurol. 2015 Jul 21. PMID: 26194197

524. Carr AS, Polke JM, Wilson J, Pelayo-Negro AL, Laura M, Nanji T, Holt J, Vaughan J, Rankin J, Sweeney MG, Blake J, Houlden H, Reilly MM. MFN2 deletion of exons 7 and 8:

51 | P a g e founder mutation in the UK population. J Peripher Nerv Syst. 2015 Jun 26. PMID: 26114802.

525. Manole A, Houlden H. Riboflavin Transporter Deficiency Neuronopathy. 2015 Jun 11. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. PMID: 26072523.

526. Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzales MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Reply: The p.Ser107Leu in BICD2 is a mutation 'hot spot' causing distal spinal muscular atrophy. Brain. 2015 Jun 10. PMID: 26063657.

527. Koutsis G, Lynch DS, Tucci A, Houlden H, Karadima G, Panas M. A novel ABCD1mutation detected by next generation sequencing in presumed hereditary spasticparaplegia: A 30-year diagnostic delay caused by misleading biochemical findings.J Neurol Sci. 2015 Aug 15;355(1-2):199-201. PMID: 26049658

528. Fratta P, Polke JM, Newcombe J, Mizielinska S, Lashley T, Poulter M, Beck J, Preza Devoy A, Sidle K, Howard R, Malaspina A, Orrell RW, Clarke J, Lu CH, MokK, Collins T, Shoaii M, Nanji T, Wray S, Adamson G, Pittman A, Renton AE, Traynor BJ, Sweeney MG, Revesz T, Houlden H, Mead S, Isaacs AM, Fisher EM. Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of theC9orf72 expansion. Neurobiol Aging. 2015 Jan;36(1):546.e1-7. PMID: 25179228

529. Koutsis G, Lynch D, Manone A, Karadima G, Reilly MM, Houlden H, Panas M.Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome in a patient with the R232C TRPV4 mutation. J Neurol. 2015 Jun 6. [Epub ahead of print] PubMed PMID: 26048687

530. Scalco RS, Gardiner AR, Pitceathly RD, Zanoteli E, Becker J, Holton JL, Houlden H, Jungbluth H, Quinlivan R. Rhabdomyolysis: a genetic perspective.Orphanet J Rare Dis. 2015 May 2;10(1):51. PMID: 25929793

531. Bettencourt C, Houlden H. Exome sequencing uncovers hidden pathways infamilial and sporadic ALS. Nat Neurosci. 2015 May;18(5):611-3. PMID: 25919956

532. Baets J, Duan X, Wu Y, Smith G, Seeley WW, Mademan I, McGrath NM, Beadell NC,Khoury J, Botuyan MV, Mer G, Worrell GA, Hojo K, DeLeon J, Laura M, Liu YT,Senderek J, Weis J, Van den Bergh P, Merrill SL, Reilly MM, Houlden H, Grossman M, Scherer SS, De Jonghe P, Dyck PJ, Klein CJ. Defects of mutant DNMT1 are linkedto a spectrum of neurological disorders. Brain. 2015 Apr;138(Pt 4):845-61. PMID: 25678562

533. Gang Q, Bettencourt C, Machado PM, Fox Z, Brady S, Healy E, Parton M, Holton JL, Hilton-Jones D, Shieh PB, Zanoteli E, De Paepe B, De Bleecker J, Shaibani A, Ripolone M, Violano R, Moggio M, Barohn RJ, Dimachkie MM, Mora M, Mantegazza R,Zanotti S, Hanna MG, Houlden H; Muscle Study Group and the International IBMGenetics Consortium. The effects of an intronic polymorphism in TOMM40 and APOEgenotypes in sporadic inclusion body myositis. Neurobiol Aging. 2015 Apr;36(4):1766.e1-3. PMID: 25670332.

534. Erro R, Hersheson J, Houlden H, Bhatia KP. A novel TUBB4A mutation suggests that genotype-phenotype correlation of H-ABC syndrome needs to be revisited. Brain. 2015 Aug;138 (Pt 8):e370. PMID: 25614026

52 | P a g e 535. Morgan S, Shoai M, Fratta P, Sidle K, Orrell R, Sweeney MG, Shatunov A,Sproviero W, Jones A, Al-Chalabi A, Malaspina A, Houlden H, Hardy J, Pittman A. Investigation of next- generation sequencing technologies as a diagnostic tool foramyotrophic lateral sclerosis. Neurobiol Aging. 2015 Mar;36(3):1600.e5-8. PMID: 25588603

536. Ernst D, Murphy SM, Sathiyanadan K, Wei Y, Othman A, Laurá M, Liu YT, PennoA, Blake J, Donaghy M, Houlden H, Reilly MM, Hornemann T. Novel HSAN1 mutation inserine palmitoyltransferase resides at a putative phosphorylation site that isinvolved in regulating substrate specificity. Neuromolecular Med. 2015 Mar;17(1):47-57. PMID: 25567748

537. Schottlaender LV, Petzold A, Wood N, Houlden H. Diagnostic clues andmanifesting carriers in fukutin-related protein (FKRP) limb-girdle muscular dystrophy. J Neurol Sci. 2015 Jan 15;348(1-2):266-8. PMID: 25560911

538. Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzalez MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T,Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML,Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain. 2015 Feb;138(Pt 2):293-310. PMID: 25497877

539. Hufnagel RB, Arno G, Hein ND, Hersheson J, Prasad M, Anderson Y, Krueger LA, Gregory LC, Stoetzel C, Jaworek TJ, Hull S, Li A, Plagnol V, Willen CM, Morgan TM, Prows CA, Hegde RS, Riazuddin S, Grabowski GA, Richardson RJ, Dieterich K, Huang T, Revesz T, Martinez-Barbera JP, Sisk RA, Jefferies C, Houlden H, Dattani MT, Fink JK, Dollfus H, Moore AT, Ahmed ZM. Neuropathy target esterase mpairments cause Oliver-McFarlane and Laurence-Moon syndromes. J Med Genet. 2015 Feb;52(2):85-94. PMID: 25480986

540. Chelban V, Lynch DS, Houlden H, Wood N. Triple trouble: a striking new phenotype or competing genes in a family with hereditary spastic paraplegia. J Neurol. 2016 Mar 30. PMID: 27025852

541. Wiethoff S, Bettencourt C, Paudel R, Madon P, Liu YT, Hersheson J, Wadia N, Desai J, Houlden H Pure Cerebellar Ataxia with Homozygous Mutations in the PNPLA6 Gene.Cerebellum. 2016 Mar 19. PMID: 26995604

542. Ramos A, Raposo M, Milà M, Bettencourt C, Houlden H, Cisneros B, Magaña JJ, Bettencourt BF, Bruges-Armas J, Santos C, Lima M. Verification of Inter-laboratorial Genotyping Consistency in the Molecular Diagnosis of Polyglutamine Spinocerebellar Ataxias. J Mol Neurosci. 2016 Jan;58(1):83-7. Epub 2015 Oct 10. PMID: 26454745

Kristjan Jessen

543. M Kipanyula, A Woodhoo, M Rhaman, D Payne, KR Jessen and R Mirsky. Calcineurin- NFAT regulation of Krox-20 expression in Schwann cells requires elevation of intracellular cyclic AMP. Journal of Neuroscience Research 91:105-115 (2013).

544. M Varela-Rey, M Iruarrizaga-Lejarreta, JJ Lozano, AM Aransay, AF Fernandez, JL Lavin, D Mósen-Ansorena, M Berdasco, M Turmaine, Z Luka, C Wagne, SC Lu, M Esteller, R Mirsky, KR Jessen, MN Fraga, ML Martínez-Chantar JM Mato, and A Woodhoo. S- adenosylmethionine Levels Regulate the Schwann Cell DNA Methylome. Neuron 81:1024- 1039 (2014)

53 | P a g e 545. KR Jessen and R Mirsky. Signalling pathways that regulate glial development and early migration-Schwann cells. Glial and Stem Cell Developmental Biology (eds.David Rowitch and Arturo Alvarez-Buylla); Comprehensive Developmental Neuroscience- Vol. 1. Elsevier BV.

546. J Hantke, L Carty, DK Wilton, S Quintes, M Koltzenburg, F Baas, R Mirsky and KR Jessen. c-Jun activation in Schwann cells protects against loss of sensory axons in inherited neuropathy. Brain. 2014 Nov;137(Pt 11):2922-37. Epub 2014 Sep 12. PMID: 25216747

Dimitri Kullmann

547. Ermolyuk YS, Alder FG, Surges R, Pavlov IY, Timofeeva Y, Kullmann DM, Volynski KE. Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels. Nat Neurosci. 2013 Dec;16(12):1754-63. Epub 2013 Nov 3. PMID: 24185424

548. Novak P, Gorelik J, Vivekananda U, Shevchuk AI, Ermolyuk YS, Bailey RJ, Bushby AJ, Moss GW, Rusakov DA, Klenerman D, Kullmann DM, Volynski KE, Korchev YE. Nanoscale-targeted patch-clamp recordings of functional presynaptic ion channels. Neuron. 2013 Sep 18;79(6):1067-77. PMID: 24050398

549. Spillane J, Higham E, Kullmann DM. Praxis (Bern 1994). 2013 May 8;102(10):603-6. Review. German. PMID: 23644246

550. Moreau AW, Kullmann DM. NMDA receptor-dependent function and plasticity in inhibitory circuits. Neuropharmacology. 2013 Nov;74:23-31. Epub 2013 Mar 26. Review. PMID: 23537500

551. Spillane J, Hayward M, Hirsch NP, Taylor C, Kullmann DM, Howard RS. Thymectomy: role in the treatment of myasthenia gravis. J Neurol. 2013 Jul;260(7):1798-801. Epub 2013 Mar 19. PMID: 23508539

552. Spillane J, Hirsch NP, Kullmann DM, Taylor C, Howard RS. Myasthenia gravis-- treatment of acute severe exacerbations in the intensive care unit results in a favourable long-term prognosis. Eur J Neurol. 2014 Jan;21(1):171-3. Epub 2013 Feb 11. PMID:23398500

553. Tomlinson SE, Rajakulendran S, Tan SV, Graves TD, Bamiou DE, Labrum RW, Burke D, Sue CM, Giunti P, Schorge S, Kullmann DM, Hanna MG. Clinical, genetic, neurophysiological and functional study of new mutations in episodic ataxia type 1. J Neurol Neurosurg Psychiatry. 2013 Oct;84(10):1107-12.. Epub 2013 Jan 24. PMID: 23349320

554. Ruiz AJ, Kullmann DM. Ionotropic receptors at hippocampal mossy fibers: roles in axonal excitability, synaptic transmission, and plasticity. Front Neural Circuits. 2013 Jan 9;6:112. eCollection 2012. PMID: 23316138

555. Akam T, Kullmann DM. Oscillatory multiplexing of population codes for selective communication in the mammalian brain. Nat Rev Neurosci. 2014 Feb;15(2):111-22. PMID: 24434912

556. Nicholson E, Kullmann DM. Long-term potentiation in hippocampal oriens interneurons: postsynaptic induction, presynaptic expression and evaluation of candidate retrograde factors. Philos Trans R Soc Lond B Biol Sci. 2013 Dec 2;369(1633):20130133. Print 2014 Jan 5. PMID: 24298136

54 | P a g e 557. Spillane J, Ermolyuk Y, Cano-Jaimez M, Lang B, Vincent A, Volynski KE, Kullmann DM. Lambert-Eaton syndrome IgG inhibits transmitter release via P/Q Ca2+ channels. Neurology. 2015 Feb 10;84(6):575-9. PubMed PMID: 25589670

558. Kullmann DM. Sodium channels open in response to depolarization and then inactivate rapidly. Brain. 2015 Apr;138(Pt 4):827 PMID: 25802315.

559. Männikkö R, Kullmann DM. Hypokalemic periodic paralysis: an omega pore mutation affects inactivation. Channels (Austin). 2015 Jun 17:0. [Epub ahead of print] PMID: 26083144

560. Spillane J, Kullmann DM, Hanna MG. Genetic neurological channelopathies: molecular genetics and clinical phenotypes. J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):37-48. Epub 2015 Nov 11. Review. PMID: 26558925.

561. Le Duigou C, Savary E, Kullmann DM, Miles R. Induction of Anti-Hebbian LTP in CA1 Stratum Oriens Interneurons: Interactions between Group I Metabotropic Glutamate Receptors and M1 Muscarinic Receptors. J Neurosci. 2015 Oct 7;35(40):13542-54. PMID: 26446209

562. Männikkö R, Kullmann DM. Hypokalemic periodic paralysis: an omega pore mutation affects inactivation. Channels (Austin). 2015;9(4):161. PMID: 26083144

563. Crisp SJ, Kullmann DM, Vincent A. Autoimmune synaptopathies. Nat Rev Neurosci. 2016 Feb;17(2):103-17. Review. PubMed PMID: 26806629.

564. Begum R, Bakiri Y, Volynski KE, Kullmann DM. Action potential broadening in a presynaptic channelopathy. Nat Commun. 2016 Jul 6;7:12102. PMID: 27381274

565. Tomlinson SE, Tan SV, Burke D, Labrum RW, Haworth A, Gibbons VS, Sweeney MG, Griggs RC, Kullmann DM, Bostock H, Hanna MG. In vivo impact of presynaptic calcium channel dysfunction on motor axons in episodic ataxia type 2. Brain. 2016 Feb;139(Pt 2):380-91. 26912519

566. Mantoan Ritter L, Macdonald DC, Ritter G, Escors D, Chiara F, Cariboni A, Schorge S, Kullmann DM, Collins M. Lentiviral expression of GAD67 and CCK -driven opsins to target interneurons in vitro and in vivo. J Gene Med. 2016 Jan;18(1-3):27-37. PMID: 26824337

567. Praschberger R, Balint B, Mencacci NE, Hersheson J, Rubio-Agusti I, Kullmann DM, Bettencourt C, Bhatia K, Houlden K. Expanding the phenotype and genetic defects associated with the GOSR2 gene. Movement Disorders Clinical Practice (in press)

568. Stödberg T, McTague A, Ruiz AJ, Hirata H, Zhen J, Long P, Farabella I, Meyer E, Kawahara A, Vassallo G, Stivaros SM, Bjursell MK, Stranneheim H, Tigerschiöld S, Persson B, Bangash I, Das K, Hughes D, Lesko N, Lundeberg J, Scott RC, Poduri A, Scheffer IE, Smith H, Gissen P, Schorge S, Reith ME, Topf M, Kullmann DM, Harvey RJ, Wedell A, Kurian MA. Loss-of-function mutations in SLC12A5, encoding the neuronal-specific potassium-chloride co-transporter KCC2, in autosomal recessive migrating partial seizures of infancy (MPSI). Nat Comm (in press)

Martin Koltzenburg

55 | P a g e 569. Rajakulendran S, Roberts J, Koltzenburg M, Hanna MG, Stewart H. Deletion of chromosome 12q21 affecting KCNC2 and ATXN7L3B in a family with neurodevelopmental delay and ataxia. J Neurol Neurosurg Psychiatry. 2013 Nov;84(11):1255-7. Epub 2013 Mar 9. PMID: 23475819

570. Hantke J, Carty L, Wagstaff LJ, Turmaine M, Wilton DK, Quintes S, Koltzenburg M, Baas F, Mirsky R, Jessen KR. R1 c-Jun activation in Schwann cells protects against axon loss in inherited neuropathy. Brain. 2014 Nov;137(Pt 11):2922-37. Epub 2014 Sep 12. PMID: 25216747

571. Corrochano S, Männikkö R, Joyce PI, McGoldrick P, Wettstein J, Lassi G, Raja Rayan DL, Blanco G, Quinn C, Liavas A, Lionikas A, Amior N, Dick J, Healy EG, Stewart M, Carter S, Hutchinson M, Bentley L, Fratta P, Cortese A, Cox R, Brown SD, Tucci V, Wackerhage H, Amato AA6, Greensmith L2, Koltzenburg M, Hanna MG, Acevedo-Arozena A1Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis. Brain. 2014 Dec;137(Pt 12):3171-85. Epub 2014 Oct 27. PMID: 25348630

572. Laurà M, Hutton EJ, Blake J, Lunn MP, Fox Z, Pareyson D, Solari A, Radice D, Koltzenburg M, Reilly MM. Pain and small fiber function in Charcot-Marie-Tooth disease type 1A. Muscle Nerve. 2014 Sep;50(3):366-71. PMID: 24395492

573. Piscosquito G, Reilly MM, Schenone A, Fabrizi GM, Cavallaro T, Santoro L, Vita G, Quattrone A, , Koltzenburg M, Padua L, Gemignani F, Visioli F, Laurà M, Calabrese D, Hughes RA, Radice D, Solari A, Pareyson D; for the CMT-TRIAAL & CMT-TRAUK Group. Is overwork weakness relevant in Charcot-Marie-Tooth disease? J Neurol Neurosurg Psychiatry. 2014 Mar 21. [Epub ahead of print] PMID: 24659795

574. Laurà M, Hutton EJ, Blake J, Lunn MP, Fox Z, Pareyson D, Solari A, Radice D, Koltzenburg M, Reilly MM. Pain and small fiber function in charcot-marie-tooth disease type 1A. Muscle Nerve. 2014 Sep;50(3):366-71. Epub 2014 May 15. PMID: 24395492

575. Mead S, Gandhi S, Beck J, Caine D, Gajulapalli D, Carswell C, Hyare H, Joiner S, Ayling H, Lashley T, Linehan JM, Al-Doujaily H, Sharps B, Revesz T, Sandberg MK, Reilly MM, Koltzenburg M, Forbes A, Rudge P, Brandner S, Warren JD, Wadsworth JD, Wood NW, Holton JL, Collinge J. A novel prion disease associated with diarrhea and autonomic neuropathy. N Engl J Med. 2013 Nov 14;369(20):1904-14. Erratum in: N Engl J Med. 2014 Jan 9;370(2):188. Gallujipali, Dillip [corrected to Gajulapalli, Dilip]. PMID: 24224623

Michael Lunn

576. Wiffen PJ, Derry S, Lunn MP, Moore RA. Topiramate for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2013 Aug 30;8:CD008314. Review. PMID: 23996081.

577. Toombs J, Paterson RW, Lunn MP, Nicholas JM, Fox NC, Chapman MD, Schott JM, Zetterberg H. Identification of an important potential confound in CSF AD studies: aliquot volume. Clin Chem Lab Med. 2013 Dec;51(12):2311-7. PMID: 23940064.

578. Marquez-Infante C, Murphy SM, Mathew L, Alsanousi A, Lunn MP, Brandner S, Yousry TA, Blake J, Reilly MM. Asymmetric sensory ganglionopathy: a case series. Muscle Nerve. 2013 Jul;48(1):145-50. Epub 2013 Jun 6. 23744601.

579. Dujmovic I, Lunn MP, Reilly MM, Petzold A. Serial cerebrospinal fluid neurofilament heavy chain levels in severe Guillain-Barré syndrome. Muscle Nerve. 2013 Jul;48(1):132-4. Epub 2013 May 29. PubMed PMID:23716297.

56 | P a g e 580. Schwingenschuh P, Saifee TA, Katschnig-Winter P, Reilly MM, Lunn MP, Manji H, Aguirregomozcorta M, Schmidt R, Bhatia KP, Rothwell JC, Edwards MJ. Cerebellar learning distinguishes inflammatory neuropathy with and without tremor. Neurology. 2013 May 14;80(20):1867-73. Epub 2013 Apr 17. PMID: 23596070

581. Nitkunan A, Lunn MP, Plant GT, Schon F. Midbrain encephalitis associated with neoplasia. Pract Neurol. 2013 Jun;13(3):178-80. Epub 2013 Mar 15. PMID: 23504030.

582. Cregg R, Laguda B, Werdehausen R, Cox JJ, Linley JE, Ramirez JD, Bodi I, Markiewicz M, Howell KJ, Chen YC, Agnew K, Houlden H, Lunn MP, Bennett DL, Wood JN, Kinali M. Novel mutations mapping to the fourth sodium channel domain of Nav1.7 result in variable clinical manifestations of primary erythromelalgia. Neuromolecular Med. 2013 Jun;15(2):265-78. Epub 2013 Jan 6. PMID: 23292638

583. Neligan A, Reilly MM, Lunn MP. CIDP: mimics and chameleons. Pract Neurol. 2014 Jul 17. [Epub ahead of print] Review. PMID: 25035142.

584. Wiffen PJ, Derry S, Moore RA, Lunn MP. Levetiracetam for neuropathic pain in adults. Cochrane Database Syst Rev. 2014 Jul 7;7:CD010943. PMID: 25000215.

585. Carvajal-González A, Leite MI, Waters P, Woodhall M, Coutinho E, Balint B, Lang B, Pettingill P, Carr A, Sheerin UM, Press R, Lunn MP, Lim M, Maddison P, Meinck HM, Vandenberghe W, Vincent A. Glycine receptor antibodies in PERM and related syndromes: characteristics, clinical features and outcomes. Brain. 2014 Aug;137(Pt 8):2178-92. Epub 2014 Jun 20. PMID: 24951641

586. Piscosquito G, Reilly MM, Schenone A, Fabrizi GM, Cavallaro T, Santoro L, Vita G, Quattrone A, Padua L, Gemignani F, Visioli F, Laurà M, Calabrese D, Hughes RA, Radice D, Solari A, Pareyson D; for the CMT-TRIAAL & CMT-TRAUK Group. Is overwork weakness relevant in Charcot-Marie-Tooth disease? J Neurol Neurosurg Psychiatry. 2014 Mar 21. [Epub ahead of print] PMID:24659795

587. Laurà M, Hutton EJ, Blake J, Lunn MP, Fox Z, Pareyson D, Solari A, Radice D, Koltzenburg M, Reilly MM. Pain and small fiber function in charcot-marie-tooth disease type 1A. Muscle Nerve. 2014 Sep;50(3):366-71. Epub 2014 May 15. PMID: 24395492.

588. Lunn MP, Hughes RA, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014 Jan 3;1:CD007115. Review. PubMed PMID: 24385423.

589. Draak TH, Vanhoutte EK, van Nes SI, Gorson KC, Van der Pol WL, Notermans NC, Nobile-Orazio E, Léger JM, Van den Bergh PY, Lauria G, Bril V, Katzberg H, Lunn MP, Pouget J, van der Kooi AJ, Hahn AF, Doorn PA, Cornblath DR, van den Berg LH, Faber CG, Merkies IS; PeriNomS Study Group. Changing outcome in inflammatory neuropathies: Rasch-comparative responsiveness. Neurology. 2014 Dec 2;83(23):2124-32. PMID: 25378677.

590. Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzińska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Am J Hum Genet. 2014 Nov 6;95(5):590-601. PMID: 25439726

57 | P a g e 591. Saifee TA, Pareés I, Kassavetis P, Kaski D, Bronstein AM, Rothwell JC, Sadnicka A, Lunn MP, Manji H, Teo JT, Bhatia KP, Reilly MM, Edwards MJ. Tremor in Charcot-Marie- Tooth disease: No evidence of cerebellar dysfunction. Clin Neurophysiol. 2015 Jan 17. pii: S1388-2457(15)00016-4 PMID: 25641441.

592. Stork AC, Lunn MP, Nobile-Orazio E, Notermans NC. Treatment for IgG and IgA paraproteinaemic neuropathy. Cochrane Database Syst Rev. 2015 Mar 24;3:CD005376. PMID: 25803231.

593. El-Tawil S, Al Musa T, Valli H, Lunn MP, Brassington R, El-Tawil T, Weber M. Quinine for muscle cramps. Cochrane Database Syst Rev. 2015 Apr 5;4:CD005044. PMID: 25842375.

594. Moore RA, Wiffen PJ, Derry S, Lunn MP. Zonisamide for neuropathic pain in adults. Cochrane Database Syst Rev. 2015 Jan 22;1:CD011241. PMID: 25879104.

595. Healy EG, Phadke R, Kidd M, Reilly MM, Lunn MP. Clinical, neuropathological and radiological evidence for a rare complication of rituximab therapy. Neuromuscul Disord. 2015 Jul;25(7):589-92. PMID: 25958339.

596. Draak TH, Vanhoutte EK, van Nes SI, Gorson KC, Van der Pol WL, Notermans NC, Nobile-Orazio E, Léger JM, Van den Bergh PY, Lauria G, Bril V, Katzberg H, Lunn MP, Pouget J, van der Kooi AJ, Hahn AF, van den Berg LH, van Doorn PA, Cornblath DR, Faber CG, Merkies IS. Comparing the NIS vs MRC and INCAT sensory scale through Rasch analyses. J Peripher Nerv Syst. 2015 Jun 25. PMID: 26110493.

597. Vanhoutte EK, P Draak TH, Gorson KC, van Nes SI, Hoeijmakers JG, Van der Pol WL, Notermans NC, Nobile-Orazio E, Léger JM, Van den Bergh PY, Lauria G, Bril V, Katzberg H, Lunn MP, Pouget J, van der Kooi AJ, Hahn AF, van Doorn PA, Cornblath DR, van den Berg LH, Faber CG, Merkies IS; PeriNomS study group. Impairment measures versus inflammatory-RODS in GBS and CIDP: A responsiveness comparison. J Peripher Nerv Syst. 2015 Jun 26. PMID: 26114893.

598. Draak TH, Pruppers MH, van Nes SI, Vanhoutte EK, Bakkers M, Gorson KC, Van der Pol WL, Notermans NC, Nobile-Orazio E, Léger JM, Van den Bergh PY, Lauria G, Bril V, Katzberg H, Lunn MP, Pouget J, van der Kooi AJ, van den Berg LH, van Doorn PA, Cornblath DR, Hahn AF, Faber CG, Merkies IS; PeriNomS study group. Grip strength comparison in immune-mediated neuropathies: Vigorimeter versus Jamar. J Peripher Nerv Syst. 2015 Jun 26. PMID: 26115516.

599. Hodkinson JP, Lucas M, Lee M, Harrison M, Lunn MP, et al. Therapeutic immunoglobulin should be dosed by clinical outcome rather than by body weight in obese patients. Clin Exp Immunol. 2015 Jul;181(1):179-87. PubMed PMID: 25731216

600. Van den Bergh PY, Lunn MP. Future needs in peripheral neuropathy outcome measures. J Peripher Nerv Syst. 2015 Sep;20(3):341-6. PMID: 26306616.

601. Draak TH, Pruppers MH, van Nes SI, Vanhoutte EK, Bakkers M, Gorson KC, Van der Pol WL, Lewis RA, Notermans NC, Nobile-Orazio E, Léger JM, Van den Bergh PY, Lauria G, Bril V, Katzberg H, Lunn MP, Pouget J, van der Kooi AJ, van den Berg LH, van Doorn PA, Cornblath DR, Hahn AF, Faber CG, Merkies IS; PeriNomS study group. Grip strength comparison in immune-mediated neuropathies: Vigorimeter vs. Jamar. J Peripher Nerv Syst. 2015 Sep;20(3):269-76. PubMed PMID: 26115516.

58 | P a g e 602. Lunn MP, Van den Bergh PY. Outcome measures in neuromuscular disease: is the world still flat? J Peripher Nerv Syst. 2015 Sep;20(3):255-9. Review. PMID: 26114965

603. Vanhoutte EK, Draak TH, Gorson KC, van Nes SI, Hoeijmakers JG, Van der Pol WL, Notermans NC, Lewis RA, Nobile-Orazio E, Léger JM, Van den Bergh PY, Lauria G, Bril V, Katzberg H, Lunn MP, Pouget J, van der Kooi AJ, Hahn AF, van Doorn PA, Cornblath DR, van den Berg LH, Faber CG, Merkies IS; PeriNomS Study Group. Impairment measures versus inflammatory RODS in GBS and CIDP: a responsiveness comparison. J Peripher Nerv Syst. 2015 Sep;20(3):289-95. PMID: 26114893.

604. Draak TH, Vanhoutte EK, van Nes SI, Gorson KC, Van der Pol WL, Notermans NC, Nobile-Orazio E, Lewis RA, Léger JM, Van den Bergh PY, Lauria G, Bril V, Katzberg H, Lunn MP, Pouget J, van der Kooi AJ, Hahn AF, van den Berg LH, van Doorn PA, Cornblath DR, Faber CG, Merkies IS; PeriNomS Study Group. Comparing the NIS vs. MRC and INCAT sensory scale through Rasch analyses. J Peripher Nerv Syst. 2015 Sep;20(3):277- 88. PubMed PMID: 26110493.

605. Lunn MP, Ellis L, Hadden RD, Rajabally YA, Winer JB, Reilly MM. A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies. J Peripher Nerv Syst. 2016 Mar;21(1):33-7. PMID: 26757367.

Jennifer Morgan

606. *Zaharieva IT, Calissano,M, Scoto M, Preston M, Cirak S, Feng L, Collins J, Kole R, Guglieri M, Straub V, Bushby K, Ferlini A, Morgan JE, Muntoni F (2013). Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne muscular Dystrophy. PLoS One 8: e80263. PMID: 24282529

607. Quattrocelli M, Crippa S, Montecchiani C, Camps J, Cornaglia AI, Boldrin L, Morgan J, Calligaro A, Casasco A, Orlacchio A, Gijsbers R, D'Hooge J, Toelen J, Janssens S, Sampaolesi M. Long-Term miR-669a Therapy Alleviates Chronic Dilated Cardiomyopathy in Dystrophic Mice. J Am Heart Assoc. 2013 Aug 20;2(4):e000284. PMID: 23963759

608. Roberts TC, Godfrey C, McClorey G, Vader P, Briggs D, Gardiner C, Aoki Y, Sargent I, Morgan JE, Wood MJ (2013). Extracellular microRNAs are dynamic non-vesicular biomarkers of muscle turnover. Nucleic Acids Res. 2013 Nov 1;41(20):9500-13. PMID: 23945935

609. Zhou H, Janghra N, Mitrpant C, Dickinson RL, Anthony K, Price L, Eperon IC, Wilton SD, Morgan J, Muntoni F (2013). A Novel Morpholino Oligomer Targeting ISS-N1 Improves Rescue of Severe Spinal Muscular Atrophy Transgenic Mice. Hum Gene Ther. 2013 Mar;24(3):331-42. PMID: 23339722

610. Boldrin L and Morgan JE (2013). Grafting of a single donor myofibre promotes hypertrophy in dystrophic mouse muscle. PloS One 2013;8(1):e54599. PMID: 23349935

611. Jonuschies J, Antoniou M, Waddington S, Boldrin L, Muntoni F, Thrasher A, Morgan J (2014). The Human Desmin Promoter Drives Robust Gene Expression for Skeletal Muscle Stem Cell-Mediated Gene Therapy. Curr Gene Ther. 2014 Jun 12. PMID: 25039614

612. *Meng J, Chun S, Asfahani R, Lochmüller H, Muntoni F, Morgan J (2014). Human skeletal muscle-derived CD133(+) cells form functional satellite cells after intramuscular transplantation in immunodeficient host mice. Mol Ther. 2014 May;22(5):1008-17. PMID: 24569833

59 | P a g e 613. *Anthony K, Arechavala-Gomeza V, Ricotti V, Torelli S, Feng L, Janghra N, Tasca G, Guglieri M, Barresi R, Armaroli A, Ferlini A, Bushby K, Straub V, Ricci E, Sewry C, Morgan J, Muntoni F (2014). Biochemical characterization of patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 skipping. JAMA Neurol. 2014 Jan;71(1):32-40. PMID: 24217213

614. Rozkalne A, Adkin C, Meng J, Lapan A, Morgan JE, Gussoni E (2014). Mouse Regenerating Myofibers Detected as False-Positive Donor Myofibers with Anti-Human Spectrin. Human Gene Therapy Jan;25(1):73-81. PMID: 24152287

615. Zaharieva IT, Thor MG, Oates EC, van Karnebeek C, Hendson G, Blom E, Witting N, Rasmussen M, Gabbett MT, Ravenscroft G, Sframeli M, Suetterlin K, Sarkozy A, D'Argenzio L, Hartley L, Matthews E, Pitt M, Vissing J, Ballegaard M, Krarup C, Slørdahl A, Halvorsen H, Ye XC, Zhang LH, Løkken N, Werlauff U, Abdelsayed M, Davis MR, Feng L, Phadke R, Sewry CA, Morgan JE, Laing NG, Vallance H, Ruben P, Hanna MG, Lewis S, Kamsteeg EJ, Männikkö R, Muntoni F. (2016), Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy. Brain. 2016 Mar;139(Pt 3):674-91. Epub 2015 Dec 22. PMID: 26700687

616. Zhou H, Meng J, Marrosu E, Janghra N, Morgan J, Muntoni F. (2015). Repeated low doses of morpholino antisense oligomer: an intermediate mouse model of spinal muscular atrophy to explore the window of therapeutic response. Hum Mol Genet. 2015 Aug 11. [Epub ahead of print] PMID: 26264577

617. Meng J, Bencze M, Asfahani R, Muntoni F, Morgan JE (2015). The effect of the muscle environment on the regenerative capacity of human skeletal muscle stem cells. Skelet Muscle. 2015 Apr 28;5:11. PMID: 25949786

618. Boldrin L, Zammit PS, Morgan JE (2015). Satellite cells from dystrophic muscle retain regenerative capacity. Stem Cell Res. 2015 Jan;14(1):20-9. PMID:25460248

619. Janghra N, Morgan JE, Sewry CA, Wilson FX, Davies KE, Muntoni F, Tinsley J. (2016). Correlation of Utrophin Levels with the Dystrophin Protein Complex and Muscle Fibre Regeneration in Duchenne and Becker Muscular Dystrophy Muscle Biopsies. PLoS One. 2016 Mar 14;11(3):e0150818. doi: 10.1371/journal.pone.0150818. eCollection 2016.

620. *Meng J, Counsell JR, Reza M, Laval SH, Danos O, Thrasher A, Lochmüller H, Muntoni F, Morgan JE. (2016) Autologous skeletal muscle derived cells expressing a novel functional dystrophin provide a potential therapy for Duchenne Muscular Dystrophy. Sci Rep. 2016 Jan 27;6:19750.

Gita Ramdharry

621. Ramdharry G, Pollard A, Anderson C, Laurá M; Murphy S; Dudziec M, Dewar E, Hutton E, Grant R, Reilly MM. A Pilot Study of Proximal Strength Training in Charcot Marie Tooth Disease. Journal of the Peripheral Nervous System,19:328-3, 2014. PMID: 25582960

622. Machado PM, Ahmed M, Brady S, Gang Q, Healy E, Morrow JM, Wallace AC, Dewar L, Ramdharry G, Parton M, Holton JL, Houlden H, Greensmith L, Hanna M (2014). Ongoing developments in sporadic inclusion body myositis. Current Rheumatology Reports, 16: 477. PMID: 25399751

623. Brouner,J, Ramdharry,G and Swann,N. (2014). An isokinetic method for inducing a localised fatigue effect in the plantar flexors and dorsiflexors of the ankle, Journal of Electromyography and Kinesiology, PMID: 25282574

60 | P a g e 624. A Hiscock, L Dewar, M Parton, P Machado, M Hanna, G Ramdharry. Frequency and circumstances of falls in people with Inclusion Body Myositis: a questionnaire survey to explore falls management and physiotherapy provision. Physiotherapy, 100 (1): 61–65, 2014. PMID: 23954023

Gipi Schiavo

625. Terenzio M, Golding M, Russell MR, Wicher KB, Rosewell I, Spencer-Dene B, Ish- Horowicz D, Schiavo G. Bicaudal-D1 regulates the intracellular sorting and signalling of neurotrophin receptors. EMBO J. 2014 Jul 17;33(14):1582-98. PMID: 24920579

626. Garrett CA, Barri M, Kuta A, Soura V, Deng W, Fisher EM, Schiavo G, Hafezparast M. DYNC1H1 mutation alters transport kinetics and ERK1/2-cFos signalling in a mouse model of distal spinal muscular atrophy. Brain. 2014 Jul;137(Pt 7):1883-93. PMID: 24755273

627. Hislop JN, Islam TA, Eleftheriadou I, Carpentier DC, Trabalza A, Parkinson M, Schiavo G, Mazarakis ND. Rabies virus envelope glycoprotein targets lentiviral vectors to the axonal retrograde pathway in motor neurons. J Biol Chem. 2014 Jun 6;289(23):16148-63. PMID: 24753246

628. Gibbs K, Greensmith L and Schiavo G (2015) Regulation of axonal transport by protein kinases. Trend Biochem Sci 40, 597-610. PMID: 26410600

629. Ahmed M, Machado P, Miller A, Spicer C, Herbelin L, He J, Noel J, Wang Y, McVey AL, Pasnoor M, Gallagher P, Statland J, Lu C-H, Kalmar B, Brady S, Sethi H, Samandouras G, Parton M, Holton JL, Weston A, Collinson L, Taylor JP, Schiavo G, Hanna MG, Barohn RJ, Dimachkie MM, Greensmith L (2016) Targeting protein homeostasis as a novel therapeutic approach in sporadic inclusion body myositis. Sci Transl Med 8, 331ra41. PMID: 27009270

630. Debaisieux S, Encheva V, Chakravarty P, Snijders AP and Schiavo G (2016) Analysis of signaling endosome composition and dynamics using SILAC in embryonic stem cell- derived motor neurons. Mol Cell Proteomics 15, 542-57. PMID: 26685126

631. Gibbs K, Kalmar B, Sleigh JN, Greensmith L and Schiavo G (2016) In vivo imaging of axonal transport in murine motor and sensory neurons. J Neurosci Meth 257, 26-33. PMID: 26424507

Stephanie Schorge

632. Burge JA, Hanna MG, Schorge S. Nongenomic actions of progesterone and 17β- estradiol on the chloride conductance of skeletal muscle. Muscle Nerve. 2013 Oct;48(4):589- 91. PMID: 23625574

633. Tomlinson SE, Rajakulendran S, Tan SV, Graves TD, Bamiou DE, Labrum RW, Burke D, Sue CM, Giunti P, Schorge S, Kullmann DM, Hanna MG. Clinical, genetic, neurophysiological and functional study of new mutations in episodic ataxia type 1. J Neurol Neurosurg Psychiatry. 2013 Oct;84(10):1107-12. PMID: 23349320

634. Bettencourt C, Ryten M, Forabosco P, Schorge S, Hersheson J, Hardy J, Houlden H; United Kingdom Brain Expression Consortium. Insights from cerebellar transcriptomic analysis into the pathogenesis of ataxia. JAMA Neurol. 2014 Jul 1;71(7):831-9. PMID: 24862029

John Thornton

61 | P a g e 635. *Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmüller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. (2013) Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PMID: 23967145

636. *Fischmann, A., Morrow, J. M., Sinclair, C. D., Reilly, M. M., Hanna, M. G., Yousry, T., Thornton, J. S. (2013). Improved anatomical reproducibility in quantitative lower-limb muscle MRI.. J Magn Reson Imaging. PMID: 24123788

637. Morrow, J. M., Matthews, E., Raja Rayan, D. L., Fischmann, A., Sinclair, C. D. J., Reilly, M. M.,Yousry, T. A. (2013). Muscle MRI reveals distinct abnormalities in genetically proven non-dystrophic myotonias. Neuromuscular Disorders. PMID: 23810313

638. Morrow, J. M., Sinclair, C. D., Fischmann, A., Reilly, M. M., Hanna, M. G., Yousry, T. A., Thornton, J. S. (2014). Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers. Eur Radiol. PMID: 24748539

639. *Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmuller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. (2014) Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross- sectional study. PMID: 24587344

Thomas Voit

640. Flanigan KM, Voit T, Rosales XQ, Servais L, Kraus JE, Wardell C, Morgan A, Dorricott S, Nakielny J, Quarcoo N, Liefaard L, Drury T, Campion G, Wright P. Pharmacokinetics and safety of single doses of drisapersen in non-ambulant subjects with Duchenne muscular dystrophy: results of a double-blind randomized clinical trial. Neuromuscul Disord. 2014 Jan;24(1):16-24. Epub 2013 Sep 11. PMID: 24321374

641. Schreckenbach T, Schröder JM, Voit T, Abicht A, Neuen-Jacob E, Roos A, Bulst S, Kuhl C, Schulz JB, Weis J, Claeys KG. Novel TPM3 mutation in a family with cap myopathy and review of the literature. Neuromuscul Disord. 2014 Feb;24(2):117-24. Epub 2013 Oct 23. Review. PMID: 24239060

642. Mademan I, Deconinck T, Dinopoulos A, Voit T, Schara U, Devriendt K, Meijers B, Lerut E, De Jonghe P, Baets J. De novo INF2 mutations expand the genetic spectrum of hereditary neuropathy with glomerulopathy. Neurology. 2013 Nov 26;81(22):1953-8. Epub 2013 Oct 30. PMID: 24174593

643. Lorain S, Peccate C, Le Hir M, Griffith G, Philippi S, Précigout G, Mamchaoui K, Jollet A, Voit T, Garcia L. Dystrophin rescue by trans-splicing: a strategy for DMD genotypes not eligible for exon skipping approaches. Nucleic Acids Res. 2013 Sep;41(17):8391-402. Epub 2013 Jul 16. PMID: 23861443

644. Mearini G, Stimpel D, Krämer E, Geertz B, Braren I, Gedicke-Hornung C, Précigout G, Müller OJ, Katus HA, Eschenhagen T, Voit T, Garcia L, Lorain S, Carrier L. Repair of Mybpc3 mRNA by 5'-trans-splicing in a Mouse Model of Hypertrophic Cardiomyopathy. Mol Ther Nucleic Acids. 2013 Jul 2;2:e102. PMID: 23820890

62 | P a g e 645. Bijlsma AY, Meskers CG, van den Eshof N, Westendorp RG, Sipilä S, Stenroth L, Sillanpää E, McPhee JS, Jones DA, Narici MV, Gapeyeva H, Pääsuke M, Voit T, Barnouin Y, Hogrel JY, Butler-Browne G, Maier AB. Diagnostic criteria for sarcopenia and physical performance. Age (Dordr). 2014 Feb;36(1):275-85. Epub 2013 Jul 2. PMID: 23818105

646. Bucher T, Colle MA, Wakeling E, Dubreil L, Fyfe J, Briot-Nivard D, Maquigneau M, Raoul S, Cherel Y, Astord S, Duque S, Marais T, Voit T, Moullier P, Barkats M, Joussemet B. scAAV9 intracisternal delivery results in efficient gene transfer to the central nervous system of a feline model of motor neuron disease. Hum Gene Ther. 2013 Jul;24(7):670-82. PMID: 23799774

647. Popplewell L, Koo T, Leclerc X, Duclert A, Mamchaoui K, Gouble A, Mouly V, Voit T, Pâques F, Cédrone F, Isman O, Yáñez-Muñoz RJ, Dickson G. Gene correction of a duchenne muscular dystrophy mutation by meganuclease-enhanced exon knock-in. Hum Gene Ther. 2013 Jul;24(7):692-701. PMID: 23790397

648. Le Hir M, Goyenvalle A, Peccate C, Précigout G, Davies KE, Voit T, Garcia L, Lorain S. AAV genome loss from dystrophic mouse muscles during AAV-U7 snRNA-mediated exon-skipping therapy. Mol Ther. 2013 Aug;21(8):1551-8. Epub 2013 Jun 11. PMID: 23752313

649. Gedicke-Hornung C, Behrens-Gawlik V, Reischmann S, Geertz B, Stimpel D, Weinberger F, Schlossarek S, Précigout G, Braren I, Eschenhagen T, Mearini G, Lorain S, Voit T, Dreyfus PA, Garcia L, Carrier L. Rescue of cardiomyopathy through U7snRNA-mediated exon skipping in Mybpc3-targeted knock-in mice. EMBO Mol Med. 2013 Jul;5(7):1128-45. Epub 2013 May 29. PMID: 23716398

650. McDonald CM, Henricson EK, Abresch RT, Florence JM, Eagle M, Gappmaier E, Glanzman AM; PTC124-GD-007-DMD Study Group, Spiegel R, Barth J, Elfring G, Reha A, Peltz S. The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study. Muscle Nerve. 2013 Sep;48(3):343-56. Epub 2013 Jun 26. PMID: 23681930

651. McDonald CM, Henricson EK, Abresch RT, Florence J, Eagle M, Gappmaier E, Glanzman AM; PTC124-GD-007-DMD Study Group, Spiegel R, Barth J, Elfring G, Reha A, Peltz SW. The 6-minute walk test and other clinical endpoints in Duchenne muscular dystrophy: reliability, concurrent validity, and minimal clinically important differences from a multicenter study. Muscle Nerve. 2013 Sep;48(3):357-68. Epub 2013 Jul 17. PMID: 23674289

652. de Lattre C, Payan C, Vuillerot C, Rippert P, de Castro D, Bérard C, Poirot I; MFM-20 Study Group. Motor function measure: validation of a short form for young children with neuromuscular diseases. Arch Phys Med Rehabil. 2013 Nov;94(11):2218-26. Epub 2013 Apr 18. PMID: 23602884

653. Vignier N, Amor F, Fogel P, Duvallet A, Poupiot J, Charrier S, Arock M, Montus M, Nelson I, Richard I, Carrier L, Servais L, Voit T, Bonne G, Israeli D. Distinctive serum miRNA profile in mouse models of striated muscular pathologies. PLoS One. 2013;8(2):e55281. Epub 2013 Feb 13. PMID: 23418438

654. Cirak S, Foley AR, Herrmann R, Willer T, Yau S, Stevens E, Torelli S, Brodd L, Kamynina A, Vondracek P, Roper H, Longman C, Korinthenberg R, Marrosu G, Nürnberg P; UK10K Consortium, Michele DE, Plagnol V, Hurles M, Moore SA, Sewry CA, Campbell KP,

63 | P a g e Voit T, Muntoni F. ISPD gene mutations are a common cause of congenital and limb-girdle muscular dystrophies. Brain. 2013 Jan;136(Pt 1):269-81. Epub 2013 Jan 3. PMID: 3288328

655. Wanschitz JV, Dubourg O, Lacene E, Fischer MB, Höftberger R, Budka H, Romero NB, Eymard B, Herson S, Butler-Browne GS, Voit T, Benveniste O. Expression of myogenic regulatory factors and myo-endothelial remodeling in sporadic inclusion body myositis. Neuromuscul Disord. 2013 Jan;23(1):75-83. Epub 2012 Oct 9. PMID: 23058947

656. Barnouin Y, Butler-Browne G, Voit T, Reversat D, Azzabou N, Leroux G, Behin A, McPhee JS, Carlier PG, Hogrel JY. Manual segmentation of individual muscles of the quadriceps femoris using MRI: a reappraisal. J Magn Reson Imaging. 2014 Jul;40(1):239-47. Epub 2013 Nov 4. PMID: 24615897

657. *Mora M, Angelini C, Bignami F, Bodin AM, Crimi M, Di Donato JH, Felice A, Jaeger C, Karcagi V, LeCam Y, Lynn S, Meznaric M, Moggio M, Monaco L, Politano L, de la Paz MP, Saker S, Schneiderat P, Ensini M, Garavaglia B, Gurwitz D, Johnson D, Muntoni F, Puymirat J, Reza M, Voit T, Baldo C, Bricarelli FD, Goldwurm S, Merla G, Pegoraro E, Renieri A, Zatloukal K, Filocamo M, Lochmüller H. The EuroBioBank Network: 10 years of hands-on experience of collaborative, transnational biobanking for rare diseases. Eur J Hum Genet. 2015 Sep;23(9):1116-23. Epub 2014 Dec 24. PMID: 25537360

658. Mearini G, Stimpel D, Geertz B, Weinberger F, Krämer E, Schlossarek S, Mourot-Filiatre J, Stoehr A, Dutsch A, Wijnker PJ, Braren I, Katus HA, Müller OJ, Voit T, Eschenhagen T, Carrier L. Mybpc3 gene therapy for neonatal cardiomyopathy enables long-term disease prevention in mice. Nat Commun. 2014 Dec 2;5:5515. PMID: 25463264.

659. Anthony K, Arechavala-Gomeza V, Taylor LE, Vulin A, Kaminoh Y, Torelli S, Feng L, Janghra N, Bonne G, Beuvin M, Barresi R, Henderson M, Laval S, Lourbakos A, Campion G, Straub V, Voit T, Sewry CA, Morgan JE, Flanigan KM, Muntoni F. Dystrophin quantification: Biological and translational research implications. Neurology. 2014 Nov 25;83(22):2062-9. Epub 2014 Oct 29. PMID: 25355828

660. Lynn S, Aartsma-Rus A, Bushby K, Furlong P, Goemans N, De Luca A, Mayhew A, McDonald C, Mercuri E, Muntoni F, Pohlschmidt M, Verschuuren J, Voit T, Vroom E, Wells DJ, Straub V. Measuring clinical effectiveness of medicinal products for the treatment of Duchenne muscular dystrophy. Neuromuscul Disord. 2015 Jan;25(1):96-105. Epub 2014 Sep 11. PMID: 25307856

661. Barthélémy I, Pinto-Mariz F, Yada E, Desquilbet L, Savino W, Silva-Barbosa SD, Faussat AM, Mouly V, Voit T, Blot S, Butler-Browne G. Predictive markers of clinical outcome in the GRMD dog model of Duchenne muscular dystrophy. Dis Model Mech. 2014 Nov;7(11):1253-61. Epub 2014 Sep 26. PMID: 25261568

662. Zimoń M, Battaloğlu E, Parman Y, Erdem S, Baets J, De Vriendt E, Atkinson D, Almeida-Souza L, Deconinck T, Ozes B, Goossens D, Cirak S, Van Damme P, Shboul M, Voit T, Van Maldergem L, Dan B, El-Khateeb MS, Guergueltcheva V, Lopez-Laso E, Goemans N, Masri A, Züchner S, Timmerman V, Topaloğlu H, De Jonghe P, Jordanova A. Unraveling the genetic landscape of autosomal recessive Charcot-Marie-Tooth neuropathies using a homozygosity mapping approach. Neurogenetics. 2015 Jan;16(1):33-42. Epub 2014 Sep 18. PMID:25231362

663. Voit T, Topaloglu H, Straub V, Muntoni F, Deconinck N, Campion G, De Kimpe SJ, Eagle M, Guglieri M, Hood S, Liefaard L, Lourbakos A, Morgan A, Nakielny J,

64 | P a g e Quarcoo N, Ricotti V, Rolfe K, Servais L, Wardell C, Wilson R, Wright P, Kraus JE. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014 Oct;13(10):987-96. Epub 2014 Sep 7. PMID: 25209738

664. Le Guiner C, Montus M, Servais L, Cherel Y, Francois V, Thibaud JL, Wary C, Matot B, Larcher T, Guigand L, Dutilleul M, Domenger C, Allais M, Beuvin M, Moraux A, Le Duff J, Devaux M, Jaulin N, Guilbaud M, Latournerie V, Veron P, Boutin S, Leborgne C, Desgue D, Deschamps JY, Moullec S, Fromes Y, Vulin A, Smith RH, Laroudie N, Barnay-Toutain F, Rivière C, Bucher S, Le TH, Delaunay N, Gasmi M, Kotin RM, Bonne G, Adjali O, Masurier C, Hogrel JY, Carlier P, Moullier P, Voit T. Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients. Mol Ther. 2014 Nov;22(11):1923-35. Epub 2014 Aug 4. PMID:25200009

665. Jeanson-Leh L, Lameth J, Krimi S, Buisset J, Amor F, Le Guiner C, Barthélémy I, Servais L, Blot S, Voit T, Israeli D. Serum profiling identifies novel muscle miRNA and cardiomyopathy-related miRNA biomarkers in Golden Retriever muscular dystrophy dogs and Duchenne muscular dystrophy patients. Am J Pathol. 2014 Nov;184(11):2885-98. Epub 2014 Sep 3. PMID: 25194663

666. Bolocan A, Quijano-Roy S, Seferian AM, Baumann C, Allamand V, Richard P, Estournet B, Carlier R, Cavé H, Gartioux C, Blin N, Le Moing AG, Gidaro T, Germain DP, Fardeau M, Voit T, Servais L, Romero NB. Congenital muscular dystrophy phenotype with neuromuscular spindles excess in a 5-year-old girl caused by HRAS mutation. Neuromuscul Disord. 2014 Nov;24(11):993-8. Epub 2014 Jun 28. PMID: 25070542

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673. Chamova T, Guergueltcheva V, Gospodinova M, Krause S, Cirak S, Kaprelyan A, Angelova L, Mihaylova V, Bichev S, Chandler D, Naydenov E, Grudkova M, Djukmedzhiev P, Voit T, Pogoryelova O, Lochmüller H, Goebel HH, Bahlo M, Kalaydjieva L, Tournev I. GNE myopathy in Roma patients homozygous for the p.I618T founder mutation. Neuromuscul Disord. 2015 Sep;25(9):713-8. Epub 2015 Jul 13. PMID: 26231298

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676. Hogrel JY, Barnouin Y, Azzabou N, Butler-Browne G, Voit T, Moraux A, Leroux G, Behin A, McPhee JS, Carlier PG. NMR imaging estimates of muscle volume and intramuscular fat infiltration in the thigh: variations with muscle, gender, and age. Age (Dordr). 2015 Jun;37(3):9798. Epub 2015 Jun 4. PMID: 26040416

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710. Galna B, Newman J, Jakovljevic DG, Bates MG, Schaefer AM, McFarland R, Turnbull DM, Trenell MI, Gorman GS, Rochester L. Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences. J Neurol. 2014 Jan;261(1):73-82. Epub 2013 Oct 23. PMID: 24150688

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714. Elson JL, Cadogan M, Apabhai S, Whittaker RG, Phillips A, Trennell MI, Horvath R, Taylor RW, McFarland R, McColl E, Turnbull DM, Gorman GS. Initial development and validation of a mitochondrial disease quality of life scale. Neuromuscul Disord. 2013 Apr;23(4):324-9. Epub 2013 Feb 20. PMID: 23433484

715. Grady JP, Campbell G, Ratnaike T, Blakely EL, Falkous G, Nesbitt V, Schaefer AM, McNally RJ, Gorman GS, Taylor RW, Turnbull DM, McFarland R. Disease progression in patients with single, large-scale mitochondrial DNA deletions. Brain. 2014 Feb;137(Pt 2):323-34. Epub 2013 Nov 25.PMID: 24277717

717. *Hall AM, Vilasi A, Garcia-Perez I, Lapsley M, Alston CL, Pitceathly RD, McFarland R, Schaefer AM, Turnbull DM, Beaumont NJ, Hsuan JJ, Cutillas PR, Lindon JC, Holmes E, Unwin RJ, Taylor RW, Gorman GS, Rahman S, Hanna MG. The urinary proteome and metabonome differ from normal in adults with mitochondrial disease. Kidney Int. 2015 Mar;87(3):610-22. Epub 2014 Sep 10. PMID: 25207879

718. Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski-Feder E, Abicht A, Czermin B, Kleinle S, Morris AA, Vassallo G, Gorman GS, Ramesh V, Turnbull DM, Santibanez-Koref M, McFarland R, Horvath R, Chinnery PF. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA. 2014 Jul 2;312(1):68-77. PMID: 25058219

719. Blakely EL, Alston CL, Lecky B, Chakrabarti B, Falkous G, Turnbull DM, Taylor RW, Gorman GS. Distal weakness with respiratory insufficiency caused by the m.8344A > G "MERRF" mutation. Neuromuscul Disord. 2014 Jun;24(6):533-6 Epub 2014 Apr 1. PMID: 24792523

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722. Ng YS, Gorman GS, Turnbull DM, Martikainen MH. The diagnosis of posterior reversible encephalopathy syndrome. Lancet Neurol. 2015 Nov;14(11):1073. PMID: 26466774.

723. Whittaker RG, Devine HE, Gorman GS, Schaefer AM, Horvath R, Ng Y, Nesbitt V, Lax NZ, McFarland R, Cunningham MO, Taylor RW, Turnbull DM. Epilepsy in adults with mitochondrial disease: A cohort study. Ann Neurol. 2015 Dec;78(6):949-57. Epub 2015 Nov 17. PMID: 26381753

724. Martikainen MH, Gorman GS, Goldsmith P, Burn DJ, Turnbull DM, Schaefer AM. Adult-onset myoclonus ataxia associated with the mitochondrial m.8993T>C "NARP" mutation. Mov Disord. 2015 Sep;30(10):1432-3. Epub 2015 Aug 12. PMID: 26265210

725. Ng YS, Grady JP, Lax NZ, Bourke JP, Alston CL, Hardy SA, Falkous G, Schaefer AG, Radunovic A, Mohiddin SA, Ralph M, Alhakim A, Taylor RW, McFarland R, Turnbull DM, Gorman GS. Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults. Eur Heart J. 2015 Jul 17. pii: ehv306. [Epub ahead of print] PMID: 26188002.

726. Gorman GS, Elson JL, Newman J, Payne B, McFarland R, Newton JL, Turnbull DM. Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease. Neuromuscul Disord. 2015 Jul;25(7):563-6. 2015 Apr 23. PMID: 26031904

727. van der Westhuizen FH, Sinxadi PZ, Dandara C, Smuts I, Riordan G, Meldau S, Malik AN, Sweeney MG, Tsai Y, Towers GW, Louw R, Gorman GS, Payne BA, Soodyall H, Pepper MS, Elson JL. Understanding the Implications of Mitochondrial DNA Variation in the Health of Black Southern African Populations: The 2014 Workshop. Hum Mutat. 2015 May;36(5):569-71. PMID: 25764011.

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732. Hardy SA, Blakely EL, Purvis AI, Rocha MC, Ahmed S, Falkous G, Poulton J, Rose MR, O'Mahony O, Bermingham N, Dougan CF, Ng YS, Horvath R, Turnbull DM, Gorman GS, Taylor RW. Pathogenic mtDNA mutations causing mitochondrial myopathy: The need for muscle biopsy. Neurol Genet. 2016 Jun 23;2(4):e82. eCollection 2016 Aug. PMID: 27536729

733. Vincent AE, Ng YS, White K, Davey T, Mannella C, Falkous G, Feeney C, Schaefer AM, McFarland R, Gorman GS, Taylor RW, Turnbull DM, Picard M. The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy. Sci Rep. 2016 Aug 10;6:30610. PMID: 27506553

734. Ng YS, Feeney C, Schaefer AM, Holmes CE, Hynd P, Alston CL, Grady JP, Roberts M, Maguire M, Bright A, Taylor RW, Yiannakou Y, McFarland R, Turnbull DM, Gorman GS. Pseudo-obstruction, stroke and mitochondrial dysfunction: A lethal combination. Ann Neurol. 2016 Jul 25. [Epub ahead of print] PMID: 27453452

735. Lax NZ, Gorman GS, Turnbull DM. Invited Review: Central nervous system involvement in mitochondrial disease. Neuropathol Appl Neurobiol. 2016 Jun 11. [Epub ahead of print] Review. PMID: 27287935

736. Martikainen MH, Ng YS, Gorman GS, Alston CL, Blakely EL, Schaefer AM, Chinnery PF, Burn DJ, Taylor RW, McFarland R, Turnbull DM. Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease. JAMA Neurol. 2016 Jun 1;73(6):668-74. PMID: 27111573

737. Kullar PJ, Quail J, Lindsey P, Wilson JA, Horvath R, Yu-Wai-Man P, Gorman GS, Taylor RW, Ng Y, McFarland R, Moore BC, Chinnery PF. Both mitochondrial DNA and mitonuclear gene mutations cause hearing loss through cochlear dysfunction. Brain. 2016 Jun;139(Pt 6):e33. Epub 2016 Mar 25. PMID: 27016405

Kieren Hollingsworth

738. Willis TA†, Hollingsworth KG†, Coombs A, Sveen ML, Andersen S, Stojkovic T, et al. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PLoS One. 2013;8(8):e70993. PMID: 23967145

739. Sinha A, Hollingsworth KG, Ball S, Cheetham T. Improving the vitamin D status of vitamin D deficient adults is associated with improved mitochondrial oxidative function in skeletal muscle. J Clin Endocrinol Metab. 2013 Mar;98(3):E509-13. PubMed PMID: 23393184

72 | P a g e 740. Hollingsworth KG†, Willis TA†, Bates MG, Dixon BJ, Lochmuller H, Bushby K, et al. Subepicardial dysfunction leads to global left ventricular systolic impairment in patients with limb girdle muscular dystrophy 2I. Eur J Heart Fail. 2013 Sep;15(9):986-94. PMID: 23576288

741. Hollingsworth KG, Higgins DM, McCallum M, Ward L, Coombs A, Straub V. Investigating the quantitative fidelity of prospectively undersampled chemical shift imaging in muscular dystrophy with compressed sensing and parallel imaging reconstruction. Magn Reson Med. 2013 Dec 17. PMID: 24347306 5. Hollingsworth KG, Garrood P, Eagle M, Bushby K, Straub V. Magnetic resonance imaging in Duchenne muscular dystrophy: longitudinal assessment of natural history over 18 months. Muscle Nerve. 2013 Oct;48(4):586-8. PMID: 23620230

742. Bates MG, Newman JH, Jakovljevic DG, Hollingsworth KG, Alston CL, Zalewski P, et al. Defining cardiac adaptations and safety of endurance training in patients with m.3243A>G-related mitochondrial disease. Int J Cardiol. 2013 Oct 9;168(4):3599-608. PMID: 23742928

743. Bates MG†, Hollingsworth KG†, Newman JH, Jakovljevic DG, Blamire AM, MacGowan GA, et al. Concentric hypertrophic remodelling and subendocardial dysfunction in mitochondrial DNA point mutation carriers. Eur Heart J Cardiovasc Imaging. 2013 Jul;14(7):650-8. PubMed PMID: 23129433

744. Willis TA†, Hollingsworth KG†, Coombs A, Sveen ML, Andersen S, Stojkovic T, et al. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross-sectional study. PLoS One. 2014;9(2):e90377. PubMed PMID: 24587344

745. Hollingsworth KG. Quantitative MRI in muscular dystrophy: An indispensable trial endpoint? Neurology. 2014 Aug 6. PMID: 25098536

746. Jakovljevic DG, Papakonstantinou L, Blamire AM, MacGowan GA, Taylor R, Hollingsworth KG, Trenell MI. Effect of physical activity on age-related changes in cardiac function and performance in women. Circ Cardiovasc Imaging. 2014 Dec 30;8(1). PMID: 25550398

747. Loughran T, Higgins DM, McCallum M, Coombs A, Straub V, Hollingsworth KG. Improving highly accelerated fat fraction measurements for clinical trials in muscular dystrophy: origin and quantitative effect of R2* changes. Radiology. 2015 May;275(2):570-8 PMID: 25575118

Rita Horvath

748. Alston CL, Schaefer AM, Raman P, Solaroli N, Krishnan KJ, Blakely EL, He L, Craig K, Roberts M, Vyas A, Nixon J, Horvath R, Turnbull DM, Karlsson A, Gorman GS, Taylor RW. Late-onset respiratory failure due to TK2 mutations causing multiple mtDNA deletions. Neurology 2013;81:2051-2053. PMID: 24198295

749. Pyle A, Griffin H, Duff J, Bennett S, Zwolinski S, Smertenko T, Yu-Wai Man P, Santibanez-Koref M, Horvath R, Chinnery PF. Late-onset sacsinopathy diagnosed by exome sequencing and comparative genomic hybridization. J Neurogenet 2013;27:176-182. PMID: 24180463

750. Gavrilova R, Horvath R. Fibroblast growth factor 21, a biomarker for mitochondrial muscle disease. (Editorial) Neurology 2013;81:1808-1809. PMID: 24142478

751. Spendiff S, Reza M, Murphy JL, Gorman G, Blakely EL, Taylor RW, Horvath R, Campbell G, Newman J, Lochmüller H, Turnbull DM. Mitochondrial DNA deletions in

73 | P a g e muscle satellite cells: implications for therapies. Hum Mol Genet 2013;22:4739-4747. PMID: 23847047

752. Spyropoulos A, Manford M, Horvath R, Alston CL, Yu-Wai-Man P, He L, Taylor RW, Chinnery PF. Near identical segregation of mtDNA heteroplasmy in blood, muscle, urinary epithelium and hair follicles in twins with optic atrophy, ptosis and intractable epilepsy. JAMA Neurol 2013;70:1552-1555. PMID: 24126373

753. *Pfeffer G, Horvath R, Klopstock T, Mootha VK, Suomalainen A, Koene S, Hirano M, Zeviani M, Bindoff LA, Yu-Wai-Man P, Hanna M, Carelli V, McFarland R, Majamaa K, Turnbull DM, Smeitink J, Chinnery PF. New treatments for mitochondrial disease-no time to drop our standards. Nat Rev Neurol 2013;9:474-481. PMID: 23817350

754. Boczonadi V, Smith PM, Pyle A, Gomez-Duran A, Schara U, Tulinius M, Chinnery PF, Horvath R. Altered 2-thiouridylation impairs mitochondrial translation in reversible infantile respiratory chain deficiency. Hum Mol Genet 2013;22(22):4602-4615. PMID: 23814040

755. Neeve VC, Pyle A, Boczonadi V, Gomez-Duran A, Griffin H, Santibanez-Koref M, Gaiser U, Bauer P, Tzschach A, Chinnery PF, Horvath R. Clinical and functional characterisation of the combined respiratory chain defect in two sisters due to autosomal recessive mutations in MTFMT. Mitochondrion 2013;13:743-748. PMID: 23499752

756. Bathgate D, Wigley R, Gorman G, Horvath R, Chinnery PF. Childhood presentation of "adult" polyglucosan body disease: normal GBE1 sequence with no glycogen branching enzyme activity. Ann Neurol 2013;73:317-318. PMID: 23526558

757. Elson JL, Cadogan M, Apabhai S, Whittaker RG, Phillips A, Trennell MI, Horvath R, Taylor RW, McFarland R, McColl E, Turnbull DM, Gorman GS. Initial development and validation of a mitochondrial disease quality of life scale. Neuromuscul Disord 2013;23:324- 329. PMID: 23433484

758. Della Marina A, Schara U, Pyle A, Möller-Hartmann C, Holinski-Feder E, Abicht A, Czermin B, Lochmüller H, Griffin H, Santibanez-Koref M, Chinnery PF, Horvath R. NDUFS8-related complex I deficiency extends phenotype from “PEO plus” to Leigh syndrome. J Inherit Metab Dis 2013;10:17-22. PMID: 23430795

759. Payne BA, Wilson IJ, Yu-Wai-Man P, Coxhead J, Deehan D, Horvath R, Taylor RW, Samuels DC, Santibanez-Koref M, Chinnery PF. Universal heteroplasmy of human mitochondrial DNA. Hum Mol Genet 2013;22:384-390. PMID: 23077218

760. Guthrie G, Pfeffer G, Bailie M, Bradshaw K, Browning AC, Horvath R, Chinnery PF, Yu-Wai-Man P. The neurological and ophthalmological manifestations of SPG4-related hereditary spastic paraplegia. J Neurol 2013;260:906-909. PMID: 23238845

761. Balreira A, Boczonadi V, Barca E, Pyle A, Bansagi B, Appleton M, Graham C, Hargreaves IP, Rasic VM, Lochmüller H, Griffin H, Taylor RW, Naini A, Chinnery PF, Hirano M, Quinzii CM, Horvath R. ANO10 mutations cause ataxia and coenzyme Q deficiency. J Neurol. 2014 Nov;261(11):2192-8. PMID: 25182700 ₁₀ 762. Herrmann DN, Horvath R, Sowden JE, Gonzalez M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmüller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S. Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. Am J Hum Genet. 2014 Sep 4;95(3):332-9. Erratum in: Am J Hum Genet. 2014 Oct 2;95(4):472. Gonzales, Michael [corrected to Gonzalez, Michael]. PubMed PMID: 25192047

74 | P a g e 763. Boczonadi V, Müller JS, Pyle A, Munkley J, Dor T, Quartararo J, Ferrero I, Karcagi V, Giunta M, Polvikoski T, Birchall D, Princzinger A, Cinnamon Y, Lützkendorf S, Piko H, Reza M, Florez L, Santibanez-Koref M, Griffin H, Schuelke M, Elpeleg O, Kalaydjieva L, Lochmüller H, Elliott DJ, Chinnery PF, Edvardson S, Horvath R. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat Commun. 2014 Jul 3;5:4287. PMID: 24989451

764. Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski- Feder E, Abicht A, Czermin B, Kleinle S, Morris AA, Vassallo G, Gorman GS, Ramesh V, Turnbull DM, Santibanez-Koref M, McFarland R, Horvath R, Chinnery PF. Use of whole- exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA. 2014 Jul 2;312(1):68-77. PMID: 25058219.

765. Bargiela D, Eglon G, Horvath R, Chinnery PF. An under-recognised cause of spastic paraparesis in middle-aged women. Pract Neurol 2014;14(3):182-184. PMID: 24154795

766. *Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzińska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Am J Hum Genet 2014;95(5):590-601. PMID:25439726

767. Boczonadi V, Müller V, Pyle A, Munkley J, Dor T, Quartararo J, Ferrero I, Karcagi V, Giunta M, Polvikoski T, Birchall D, Princzinger A, Cinnamon Y, Lützkendorf S, Piko H, Reza M, Florez L, Santibanez-Koref M, Griffin H, Schuelke M, Elpeleg O, Kalaydjieva L, Lochmüller H, Elliott DJ, Chinnery PF, Edvardson S and Horvath R. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat Commun 2014;5:4287. PMID: 24989451

768. Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski- Feder E, Abicht A, Czermin B, Kleinle S, Morris AAM, Vassallo G, Gorman GS, Turnbull DM, Ramesh V, Santibanez-Koref M, McFarland R, Horvath R (joint last author), Chinnery PF. Whole exome sequencing defines the genetic basis of multiple mitochondrial respiratory chain complex deficiency. JAMA 2014 Jul 2;312(1):68-77. PMID: 25058219

769. Hermann DN, Horvath R (joint first author), Sowden JE, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmüller H, Griffin H, Chinnery PF, Gonzales M, Sanchez-Mejias A, Lloyd TE, Littleton JT, Zuchner S. Mutations in Synaptotagmin 2 cause an autosomal dominant form of Lambert-Eaton myasthenic syndrome and non-progressive motor neuropathy Am J Hum Genet, August 2014. PMID: 25192047

770. Balreira A, Boczonadi V, Barca E, Pyle A, Bansagi B, Appleton M, Graham C, Hargreaves IP, Rasic VM, Lochmüller H, Griffin H, Taylor RW, Naini A, Chinnery PF, Hirano M, Quinzii CM, Horvath R. ANO10 mutations cause ataxia and coenzyme Q10 deficiency. J Neurol 2014 Sep 3. [Epub ahead of print]. PMID: 25182700

771. Pyle A, Ramesh V, Bartsakoulia M, Boczonadi V, Gomez-Duran A, Herczegfalvi A, Blakely EL, Smertenko T, Duff J, Moore D, Yu Wai Man P, Douroudis K, Santibanez-Koref M, Griffin H, Lochmüller H, Karcagi V, Taylor RW, Chinnery PF, Horvath R. Behr`s syndrome is a characteristic clinical presentation of disturbed mitochondrial translation

75 | P a g e caused by mutations in the C12orf65 gene. J Neuromuscul Disease. 1(1):55-6 July 2014. PMID: 26380172

772. Chaouch A, Porcelli V, Cox D, Edvardson S, Scarcia P, De Grassi A, Pierri CL, Cossins J, Laval SH, Griffin H, Müller JS, Evangelista T, Töpf A, Abicht A, Huebner A, von der Hagen M, Bushby K, Straub V, Horvath R, Elpeleg O, Palace J, Senderek J, Beeson D, Palmieri L and Lochmüller H. Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. J Neuromusc Disease. July 2014. PMID: 26870663

773. Griffin HR, Pyle A, Duff J, Hudson G, Horvath R, Wilson JI, Santibanez-Koref M, Taylor RW, Chinnery PF. Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations. Genetics in Medicine. 2014 Jun 5. [Epub ahead of print]. PMID: 24901348

774. Gorman GS, Pfeffer G, Griffin H, Blakely EL Kurzawa-Akanbi M, Gabriel J, Sitarz K, Roberts M, Schoser B, Pyle A, Schaefer AM, McFarland R, Turnbull DM, Horvath R, Chinnery PF, Taylor RW. Clonal expansion of secondary mtDNA deletions associated with spinocerebellar ataxia type 28, JAMA Neurology in press May 2014. PMID: 25420100

775. Gardner K, Payne B, Horvath R, Chinnery PF. Use of stereotypical mutational motifs to define resolution limits for the ultra-deep resequencing of mitochondrial DNA. Eur. J. Hum Gen 2014 Jun 4. PMID: 24896153

776. Sitarz KS, Elliott HR, Karaman BS, Relton C, Chinnery PF, Horvath R. Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts. Mol Genet Metab 2014;112:57-63. PMID: 24725338

777. Chaouch A, Brennan KM, Hudson J, Longman C, McConville J, Morrison PJ, Farrugia ME, Petty R, Stewart W, Norwood F, Horvath R, Chinnery PF, Costigan D, Winer J, Polvikoski T, Healy E, Sarkozy A, Evangelista T, Pogoryelova O, Eagle M, Bushby K, Straub V, Lochmüller H. Two recurrent mutations are associated with GNE myopathy in the North of Britain. J Neurol Neurosurg Psychiatry. 2014 Apr 2. PMID: 24695763

778. Nightingale H, Pfeffer G, Horvath R. Chronic and slowly progressive weakness of the legs and hands. BMJ 2014 Jan 28;348:g459. PMID: 24473995

779. Pfeffer G, Gorman GS, Griffin H, Kurzawa-Akanbi M, Blakely EL, Wilson I, Sitarz K, Moore D, Murphy JL, Alston CL, Pyle A, Coxhead J, Payne B, Gorrie GH, Longman C, Hadjivassiliou M, McConville J, Dick D, Imam I, Hilton D, Norwood F, Baker MR, Jaiser SR, Yu-Wai-Man P, Farrell M, McCarthy A, Lynch T, McFarland R, Schaefer AM, Turnbull DM, Horvath R, Taylor RW, Chinnery PF. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. Brain 2014;137(Pt 5):1323-1336. PMID: 24727571

780. Remenyi V, Inczedy-Farkas G, Komlosi K, Horvath R, Maasz A, Janicsek I, Pentelenyi K, Gal A, Karcagi V, Melegh B, Molnar MJ. Retrospective assessment of the most common mitochondrial DNA mutations in a large Hungarian cohort of suspect mitochondrial cases. Mitochondrial DNA 2014 Jan 17. [Epub ahead of print]. PMID: 24438288

781. Boczonadi V, Horvath R. Mitochondria: Impaired mitochondrial translation in human disease. Int J Biochem Cell Biol 2014;48:77-84. PMID: 24412566

782. *Foley AR, Menezes MP, Pandraud A, Gonzalez MA, Al-Odaib A, Abrams AJ, Sugano K, Yonezawa A, Manzur AY, Burns J, Hughes I, McCullagh BG, Jungbluth H, Lim MJ, Lin JP, Megarbane A, Urtizberea JA, Shah AH, Antony J, Webster R, Broomfield A, Ng J, Mathew AA, O'Byrne JJ, Forman E, Scoto M, Prasad M, O'Brien K, Olpin S, Oppenheim M,

76 | P a g e Hargreaves I, Land JM, Wang MX, Carpenter K, Horvath R, Straub V, Lek M, Gold W, Farrell MO, Brandner S, Phadke R, Matsubara K, McGarvey ML, Scherer SS, Baxter PS, King MD, Clayton P, Rahman S, Reilly MM, Ouvrier RA, Christodoulou J, Züchner S, Muntoni F, Houlden H. Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain 2014;137(Pt 1):44-56. PMID: 24253200

783. Pfeffer G, Barresi R, Wilson I, Hardy SA, Griffin H, Hudson J, Radunovic A, Winer J, Vaydia S, Raman A, Busby M, Straub V, Horvath R, Bushby K, Lochmüller H, Chinnery PF, Sarkozy A. Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure. J Neurol Neurosurg Psychiatry 2014;85:331-338. PMID:23486992

784. Pfeffer G, Griffin H, Pyle A, Horvath R, Chinnery PF. Reply: Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain. Brain 2014;137(Pt 4):e271. PMID: 24271327

785. Bargiela D, Shanmugarajah P, Lo C, Blakely EL, Taylor RW, Horvath R, Wharton S, Chinnery PF, Hadjivassiliou M. Mitochondrial pathology in progressive cerebellar ataxia. Cerebellum Ataxias 2015;2:16. PMID: 26640698

786. Whittaker RG, Herrmann DN, Bansagi B, Hasan BA, Lofra RM, Logigian EL, Sowden JE, Almodovar JL, Littleton JT, Zuchner S, Horvath R (joint last author), Lochmüller H. Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome. Neurology 2015;85:1964-1971. PMID: 26519543

787. Whittaker RG, Devine HE, Gorman GS, Schaefer AM, Horvath R, Ng Y, Nesbitt V, Lax NZ, McFarland R, Cunningham MO, Taylor RW, Turnbull DM. Epilepsy in adults with mitochondrial disease: A cohort study. Ann Neurol 2015;78:949-957. PMID: 26381753

788. Gorman GS, Pfeffer G, Griffin H, Blakely EL, Kurzawa-Akanbi M, Gabriel J, Sitarz K, Roberts M, Schoser B, Pyle A, Schaefer AM, McFarland R, Turnbull DM, Horvath R, Chinnery PF, Taylor RW. Clonal expansion of secondary mitochondrial DNA deletions associated with spinocerebellar ataxia type 28. JAMA Neurol. 2015 Jan;72(1):106-11. PMID: 25420100.

789. Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, Taylor RW, Turnbull DM, McFarland R.Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015 May;77(5):753-9. PMID: 25652200.

790. Boczonadi V, Giunta M, Lane M, Tulinius M, Schara U, Horvath R. Investigating the role of the physiological isoform switch of cytochrome c oxidase subunits in reversible mitochondrial disease. Int J Biochem Cell Biol. 2015 Jun;63:32-40. PMID: 25666558.

791. Payne BA, Gardner K, Blakely EL, Maddison P, Horvath R, Taylor RW, Chinnery PF. Clinical and pathological features of mitochondrial DNA deletion disease following antiretroviral treatment. JAMA Neurol. 2015 May;72(5):603-5 PMID: 25961175.

792. Horvath R, Chinnery PF. Nuclear-mitochondrial proteins: too much to process? Brain. 2015 Jun;138(Pt 6):1451-3. PMID: 26013806.

793. Bargiela D, Yu-Wai-Man P, Keogh M, Horvath R, Chinnery PF. Prevalence of neurogenetic disorders in the North of England. Neurology 2015;85:1195-1201. PMID: 26341866

794. Braczynski AK, Vlaho S, Müller K, Wittig I, Blank AE,Tews DS, Drott U, Kleinle S, Abicht A, Horvath R, Plate KH, Stenzel W, Goebel HH, Schulze A, Harter PN, Kieslich M, Mittelbronn M. ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural

77 | P a g e mitochondrial degeneration and is amenable to treatment. Biomed Res Int 2015;2015:462592. PMID: 26550569

795. Köhler C, Heyer C, Hoffjan S, Stemmler S, Lücke T, Thiels C, Kohlschütter A, Löbel U, Horvath R, Kleinle S, Benet-Pages A, Abicht A. Early-onset leukoencephalopathy due to a homozygous missense mutation in the DARS2 gene. Mol Cell Probes 2015;29:319-322.

796. Mueller JM, Giunta M, Horvath R. Exosomal Protein Deficiencies: How Abnormal RNA Metabolism Results in Childhood-Onset Neurological Diseases. J Neuromusc Diseases 2015;2:31-37. PMID: 27127732

797. Keogh M, Steel H, Horvath R, Chinnery PF. Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia. J Neurol 2015;262:1822-1827. PMID: 25976027

798. Horvath R, Chinnery PF. Modifying mitochondrial tRNAs: delivering what the cell needs. Cell Metab 2015;21:351-352. PMID: 25738451

799. Boczonadi V, Bansagi B, Horvath R. Reversible infantile mitochondrial diseases. J Inherit Metab Dis. 2015;38(3):427-435. PMID: 25407320

800. Keogh MJ, Aribisala BS, He J, Tulip E, Butteriss D, Morris C, Gorman G, Horvath R, Chinnery PF, Blamire AM. Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity. J Neurol. 2015 in press, July 2015. PMID: 26142024

801. Bansagi B, Antoniadi T, Burton-Jones S, Murphy SM, McHugh J, Alexander M, Wells R, Davies J, Hilton-Jones D, Lochmüller H, Chinnery PF, Horvath R. Genotype/phenotype correlations in AARS-related neuropathy in a cohort of patients from the United Kingdom and Ireland. J Neurol. May 2015. PMID: 26032230

802. Bansagi B, Griffin H, Ramesh V, Duff J, Pyle A, Chinnery PF, Horvath R. The p.Ser107Leu in BICD2 is a mutation “hot spot” causing distal spinal muscular atrophy. Brain. April 2015. PMID: 26063656

803. Pyle A, Nightingale HJ, Griffin H, Abicht A, Kirschner J, Baric I, Cuk M, Douroudis K, Feder L, Kratz M, Czermin B, Kleinle S, Santibanez-Koref M, Karcagi V, Holinski-Feder E, Chinnery PF, Horvath R. Respiratory chain deficiency in non-mitochondrial disease. Neurology Genetics. April 2015. PMID: 27066545

804. Daud D, Griffin H, Douroudis K, Kleinle S, Eglon G, Pyle A, Patrick F. Chinnery, Horvath R. Whole exome sequencing and the clinician: clinical skills and functional validation are important in variant filtering. J Neurol 2015 May 10. [Epub ahead of print]. PMID: 25957632

805. Pyle A, Griffin H, Keogh MJ, Horvath R, Chinnery PF. Reply: Evaluation of exome sequencing variation in undiagnosed ataxias. Brain 2015 Apr 4. [Epub ahead of print]. PMID: 25842392

806. Boczonadi V , Giunta M, Lane M, Tulinius M, Schara U, Horvath R. Investigating the role of the physiological isoform switch of cytochrome c oxidase subunits in reversible mitochondrial disease. Int J Biochem Cell Biol 2015;63:32-40. PMID: 25666558

807. Evangelista T, Bansagi B,Pyle A, Griffin H, Douroudis K, Polvikoski P, Antoniadi T, Bushby K, Straub V, Chinnery PF, Lochmüller H, Horvath R. Phenotypic variability of TRPV4 related neuropathies. Neuromusc Disord 2015 Mar 18. [Epub ahead of print]. PMID: 25900305

78 | P a g e 808. Pfeffer G, Pyle A, Griffin H, Miller J, Wilson V, Turnbull L, Fawcett K, Sims D, Eglon G, Hadjivassiliou M, Horvath R, Németh A, Chinnery PF. SPG7 mutations are a common cause of undiagnosed ataxia. Neurology 2015;84:1174-1176. PMID: 25681447

809. Payne BA, Gardner K, Maddison P, Horvath R, Taylor RW, Price AD, Chinnery PF. Clinical and pathological features of mitochondrial DNA deletion disease following anti- retroviral treatment JAMA Neurol 2015;72:603-605. PMID: 25961175

810. Euro L, Konovalova S, Cayuela JA, Tulinius M, Griffin H, Horvath R, Taylor RW, Chinnery PF, Schara U, Thorburn DR, Suomalainen A, Chihade J, Tyynismaa H. Structural modeling of tissue-specific mitochondrial alanyl-tRNA synthetase (AARS2) defects predicts differential effects on aminoacylation. Frontiers in Genetics, 2015;6:21. PMID: 25705216

811. Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, Taylor RW, Turnbull DM, McFarland R. Prevalence of nuclear and mtDNA mutations related to adult mitochondrial disease. Annals of Neurology 2015;77:753-759. PMID: 25652200

812. Pyle A, Smertenko T, Bargiela D, Griffin H, Duff J, Appleton M, Douroudis K, Pfeffer G, Santibanez-Koref M, Eglon G, Yu-Wai-Man P, Ramesh V, Horvath R (joint last author), Chinnery PF. Exome sequencing in undiagnosed inherited and sporadic ataxias. Brain 2015;138(Pt 2):276-283. PMID: 25497598

813. Zurita Rendon O, Antonicka H, Horvath R, Shoubridge EA. A mutation in the FAD- dependent oxidoreductase FOXRED1 results in cell-type specific assembly defects in oxidative phosphorylation complexes I and II. Mol Cell Biol. 2016. PMID: 27215383

814. Wilson IJ, Carling PJ, Alston CL, Floros VI, Pyle A, Hudson G, Sallevelt SC, Lamperti C, Carelli V, Bindoff LA, Samuels DC, Wonnapinij P, Zeviani M, Taylor RW, Smeets HJ, Horvath R, Chinnery PF. Mitochondrial DNA sequence characteristics modulate the size of the genetic bottleneck. Hum Mol Genet. 2016;25:1031-1041. PMID: 26740552

815. Olsen RK, Konarikova E, Giancaspero TA, Mosegaard S, Boczonadi V, Matakovic L, Veauville-Merllie A, Terrile C, Schwarzmayr T, Haack TB, Auranen M, Leone P, Galluccio M, Imbard A, Gutierrez-Rios P, Palmfeldt J, Graf E, Vianey-Saban C, Oppenheim M, Schiff M, Pichard S, Rigal O, Pyle A, Chinnery PF, Konstantopoulou V, Moslinger D, Feichtinger RG, Talim B, Topaloglu H, Coskun T, Gucer S, Botta A, Pegoraro E, Malena A, Vergani L, Mazza D, Zollino M, Ghezzi D, Acquaviva C, Tyni T, Boneh A, Meitinger T, Strom TM, Gregersen N, Mayr JA, Horvath R, Barile M, Prokisch H. Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency. Am J Hum Genet. 2016;98:1130-1145. PMID: 27259049

816. Nightingale H, Pfeffer G, Bargiela D, Horvath R, Chinnery PF. Emerging therapies for mitochondrial disorders. Brain. 2016;139:1633-1648. PMID: 27190030

817. Lewis-Smith D, Kamer KJ, Griffin H, Childs AM, Pysden K, Titov D, Duff J, Pyle A, Taylor RW, Yu-Wai-Man P, Ramesh V, Horvath R, Mootha VK, Chinnery PF. Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood. Neurol Genet. 2016;2:e59. PMID: 27123478

818. Kullar PJ, Quail J, Lindsey P, Wilson JA, Horvath R, Yu-Wai-Man P, Gorman GS, Taylor RW, Ng Y, McFarland R, Moore BC, Chinnery PF. Both mitochondrial DNA and mitonuclear gene mutations cause hearing loss through cochlear dysfunction. Brain. 2016;139:e33. PMID: 27016405

79 | P a g e 819. Giunta M, Edvardson S, Xu Y, Schuelke M, Gomez-Duran A, Boczonadi V, Elpeleg O, Muller JS, Horvath R. Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy. Hum Mol Genet. 2016. PMID: 27193168

820. Claeys KG, Abicht A, Hausler M, Kleinle S, Wiesmann M, Schulz JB, Horvath R, Weis J. Novel genetic and neuropathological insights in NARP. Muscle Nerve. 2016. PMID: 20715314

821. Boczonadi V, Horvath R. Amyloid-beta in mitochondrial disease: mutation in a human metallopeptidase links amyloidotic neurodegeneration with mitochondrial processing. EMBO Mol Med. 2016;8:173-175. PMID: 26813924

822. Hardy S, Blakely EL, Purvis AI, Rocha MC, Ahmed S, Falkous G, Poulton J, Rose MR, O’Mahoney O, Bermingham N, Dougan CF, Ng YS, Horvath R, Turnbull DM, Gorman GS, Taylor RW. Pathogenic mtDNA mutations causing mitochondrial myopathy: still the need to muscle biopsy. Neurology Genetics May 2016 PMID: 27536729

Hanns Lochmüller

823. Zoltowska K, Webster R, Finlayson S, Maxwell S, Cossins J, Muller J, Lochmüller H, Beeson D. Mutations in GFPT1 that underlie limb-girdle congenital myasthenic syndrome result in reduced cell-surface expression of muscle AChR. Hum Mol Genet. 2013; 22(14):2905-13. PMID: 23569079.

824. *Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M,Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Bushby K, Lochmüller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PLoS One. 2013; 8(8):e70993. PMID: 23967145.

825. Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Muller- Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmüller H. Treatment of dysferlinopathy with deflazacort: a double-blind, placebo- controlled clinical trial. Orphanet J Rare Dis. 2013; 826. PMID: 23406536.

826. Wagner M, Chaouch A, Muller JS, Polvikoski T, Willis TA, Sarkozy A, Eagle M, Bushby K, Straub V, Lochmüller H. Presymptomatic late-onset Pompe disease identified by the dried blood spot test. Neuromuscul Disord. 2013; 23(1):89-92. PMID: 23062590.

827. *Turner C, Hilton-Jones D, Lochmüller H, Hanna MG. MRC Centre for Neuromuscular Diseases 1st (1st December 2010), and 2nd (2nd May 2012) myotonic dystrophy workshops, London, UK and the myotonic dystrophy standards of care and national registry meeting, Newcastle, UK July 2011. Neuromuscul Disord. 2013; 23(12):1069-80. PMID: 24054840.

828. Tremblay JP, Xiao X, Aartsma-Rus A, Barbas C, Blau HM, Bogdanove AJ, Boycott K, Braun S, Breakefield XO, Bueren JA, Buschmann M, Byrne BJ, Calos M, Cathomen T, Chamberlain J, Chuah M, Cornetta K, Davies KE, Dickson JG, Duchateau P, Flotte TR, Gaudet D, Gersbach CA, Gilbert R, Glorioso J, Herzog RW, High KA, Huang W, Huard J, Joung JK, Liu D, Liu D, Lochmüller H, Lustig L, Martens J, Massie B, Mavilio F, Mendell JR, Nathwani A, Ponder K, Porteus M, Puymirat J, Samulski J, Takeda S, Thrasher A, VandenDriessche T, Wei Y, Wilson JM, Wilton SD, Wolfe JH, Gao G. Translating the genomics revolution: the need for an international gene therapy consortium for monogenic diseases. Mol Ther. 2013; 21(2):266-8. PMID: 23369965.

829. Spendiff S, Reza M, Murphy JL, Gorman G, Blakely EL, Taylor RW, Horvath R, Campbell G, Newman J, Lochmüller H, Turnbull DM. Mitochondrial DNA deletions in

80 | P a g e muscle satellite cells: implications for therapies. Hum Mol Genet. 2013; 22(23):4739-47. PMID: 23847047.

830. *Sarkozy A, Hicks D, Hudson J, Laval SH, Barresi R, Hilton-Jones D, Deschauer M, Harris E, Rufibach L, Hwang E, Bashir R, Walter MC, Krause S, van den Bergh P, Illa I, Penisson-Besnier I, De Waele L, Turnbull D, Guglieri M, Schrank B, Schoser B, Seeger J, Schreiber H, Glaser D, Eagle M, Bailey G, Walters R, Longman C, Norwood F, Winer J, Muntoni F, Hanna M, Roberts M, Bindoff LA, Brierley C, Cooper RG, Cottrell DA, Davies NP, Gibson A, Gorman GS, Hammans S, Jackson AP, Khan A, Lane R, McConville J, McEntagart M, Al-Memar A, Nixon J, Panicker J, Parton M, Petty R, Price CJ, Rakowicz W, Ray P, Schapira AH, Swingler R, Turner C, Wagner KR, Maddison P, Shaw PJ, Straub V, Bushby K, Lochmüller H. ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation. Hum Mutat. 2013; 34(8):1111-8. PMID: 23606453.

831. Rodger S, Lochmüller H, Tassoni A, Gramsch K, Konig K, Bushby K, Straub V, Korinthenberg R, Kirschner J. The TREAT-NMD care and trial site registry: an online registry to facilitate clinical research for neuromuscular diseases. Orphanet J Rare Dis. 2013; 8171. PMID: 24148153.

832. Pfeffer G, Barresi R, Wilson IJ, Hardy SA, Griffin H, Hudson J, Elliott HR, Ramesh AV, Radunovic A, Winer J, Vaidya S, Raman A, Busby M, Farrugia ME, Ming A, Everett C, Emsley HCA, Horvath R, Straub V, Bushby K, Lochmüller H, Chinnery P, Sarkozy A. A founder mutation in the titin gene is a common cause of myofibrillar myopathy with early respiratory failure. Neuromuscular Disorders. 2013; 23(9-10):820-. PMID: 23486992

833. Pertl C, Eblenkamp M, Pertl A, Pfeifer S, Wintermantel E, Lochmüller H, Walter MC, Krause S, Thirion C. A new web-based method for automated analysis of muscle histology. BMC Musculoskelet Disord. 2013; 1426. PMID: 23324401.

834. Marina AD, Schara U, Pyle A, Moller-Hartmann C, Holinski-Feder E, Abicht A, Czermin B, Lochmüller H, Griffin H, Santibanez-Koref M, Chinnery PF, Horvath R. NDUFS8-related Complex I Deficiency Extends Phenotype from "PEO Plus" to Leigh Syndrome. JIMD Rep. 2013; 1017-22. PMID: 23430795.

835. *Mahjneh I, Lochmüller H, Muntoni F, Abicht A. DOK7 limb-girdle myasthenic syndrome mimicking congenital muscular dystrophy. Neuromuscul Disord. 2013; 23(1):36- 42. PMID: 22884442.

836. Lorenzoni PJ, Scola RH, Kay CS, Lochmüller H, Werneck LC. Congenital myasthenic syndrome and minicore-like myopathy with DOK7 mutation. Muscle Nerve. 2013; 48(1):151- 2. PMID: 23657916.

837. Lorenzoni PJ, Scola RH, Kay CS, Filla L, Miranda AP, Pinheiro JM, Chaouch A, Lochmüller H, Werneck LC. Salbutamol therapy in congenital myasthenic syndrome due to DOK7 mutation. J Neurol Sci. 2013; 331(1-2):155-7. PMID: 23790237.

838. Klymiuk N, Blutke A, Graf A, Krause S, Burkhardt K, Wuensch A, Krebs S, Kessler B, Zakhartchenko V, Kurome M, Kemter E, Nagashima H, Schoser B, Herbach N, Blum H, Wanke R, Aartsma-Rus A, Thirion C, Lochmüller H, Walter MC, Wolf E. Dystrophin- deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle. Hum Mol Genet. 2013; 22(21):4368-82. PMID: 23784375.

839. Hornsey MA, Laval SH, Barresi R, Lochmüller H, Bushby K. Muscular dystrophy in dysferlin-deficient mouse models. Neuromuscul Disord. 2013; 23(5):377-87. PMID: 23473732.

81 | P a g e 840. Hollingsworth KG, Willis TA, Bates MGD, Dixon BJ, Lochmüller H, Bushby K, Bourke J, MacGowan GA, Straub V. Subepicardial dysfunction leads to global left ventricular systolic impairment in patients with limb girdle muscular dystrophy 2I. European Journal of Heart Failure. 2013; 15(9):986-94. PMID: WOS:000323575700006. PMID: 23576288

841. Harris E, Laval S, Hudson J, Barresi R, De Waele L, Straub V, Lochmüller H, Bushby K, Sarkozy A. Undiagnosed genetic muscle disease in the north of England: an in depth phenotype analysis. PLoS Curr. 2013; 5. PMID: 23788081.

842. Hammond E, Watts GF, Rubinstein Y, Farid W, Livingston M, Knowles JW, Lochmüller H, Bellgard M, Dawkins HJ. Role of international registries in enhancing the care of familial hypercholesterolaemia. Int J Evid Based Healthc. 2013; 11(2):134-9. PMID: 23750577.

843. Dick E, Kalra S, Anderson D, George V, Ritso M, Laval SH, Barresi R, Aartsma-Rus A, Lochmüller H, Denning C. Exon skipping and gene transfer restore dystrophin expression in human induced pluripotent stem cells-cardiomyocytes harboring DMD mutations. Stem Cells Dev. 2013; 22(20):2714-24. PMID: 23829870.

844. Cossins J, Belaya K, Hicks D, Salih MA, Finlayson S, Carboni N, Liu WW, Maxwell S, Zoltowska K, Farsani GT, Laval S, Seidhamed MZ, Consortium WGS, Donnelly P, Bentley D, McGowan SJ, Muller J, Palace J, Lochmüller H, Beeson D. Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. Brain. 2013; 136(Pt 3):944-56. PMID: 23404334.

845. Bladen CL, Rafferty K, Straub V, Monges S, Moresco A, Dawkins H, Roy A, Chamova T, Guergueltcheva V, Korngut L, Campbell C, Dai Y, Barisic N, Kos T, Brabec P, Rahbek J, Lahdetie J, Tuffery-Giraud S, Claustres M, Leturcq F, Ben Yaou R, Walter MC, Schreiber O, Karcagi V, Herczegfalvi A, Viswanathan V, Bayat F, de la Caridad Guerrero Sarmiento I, Ambrosini A, Ceradini F, Kimura E, van den Bergen JC, Rodrigues M, Roxburgh R, Lusakowska A, Oliveira J, Santos R, Neagu E, Butoianu N, Artemieva S, Rasic VM, Posada M, Palau F, Lindvall B, Bloetzer C, Karaduman A, Topaloglu H, Inal S, Oflazer P, Stringer A, Shatillo AV, Martin AS, Peay H, Flanigan KM, Salgado D, von Rekowski B, Lynn S, Heslop E, Gainotti S, Taruscio D, Kirschner J, Verschuuren J, Bushby K, Beroud C, Lochmüller H. The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia. Hum Mutat. 2013; 34(11):1449-57. PMID: 23913485.

846. *Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmüller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross- sectional study. PLoS One. 2014; 9(2):e90377. PMID: 24587344.

847. Webster R, Liu WW, Chaouch A, Lochmüller H, Beeson D. Fast-channel congenital myasthenic syndrome with a novel acetylcholine receptor mutation at the alpha-epsilon subunit interface. Neuromuscul Disord. 2014; 24(2):143-7. PMID: 24295813.

848. Walter MC, Bernert G, Zimmermann U, Mullner-Eidenbock A, Moser E, Kalaydjieva L, Lochmüller H, Muller-Felber W. Long-term follow-up in patients with CCFDN syndrome. Neurology. 2014; 83(15):1337-44. PMID: 25186864.

849. *Van den Bergen JC, Hiller M, Bohringer S, Vijfhuizen L, Ginjaar HB, Chaouch A, Bushby K, Straub V, Scoto M, Cirak S, Humbertclaude V, Claustres M, Scotton C, Passarelli C, Lochmüller H, Muntoni F, Tuffery-Giraud S, Ferlini A, Aartsma-Rus AM, Verschuuren JJ, t Hoen PA, Spitali P. Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants. J Neurol Neurosurg Psychiatry. 2014. PMID: 25476005.

82 | P a g e 850. Thompson R, Johnston L, Taruscio D, Monaco L, Beroud C, Gut IG, Hansson MG, t Hoen PB, Patrinos GP, Dawkins H, Ensini M, Zatloukal K, Koubi D, Heslop E, Paschall JE, Posada M, Robinson PN, Bushby K, Lochmüller H. RD-Connect: an integrated platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research. J Gen Intern Med. 2014; 29 Suppl 3S780-7. PMID: 25029978.

851. Pyle A, Ramesh AV, Bartsakoulia M, Boczonadi V, Gomez-Duran A, Herczegfalvi A, Blakely E, Smertenko T, Duff J, Eglon G, Moore D, Yu Waiman P, Douroudis K, Santibanez Koref M, Griffin H, Lochmüller H, Karcagi V, Taylor R, Chinnery P, Horvath R. Behr's Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in the C12orf65 Gene. J Neuromusc Dis. 2014; 1(1):55-63.

852. Pfeffer G, Barresi R, Wilson IJ, Hardy SA, Griffin H, Hudson J, Elliott HR, Ramesh AV, Radunovic A, Winer JB, Vaidya S, Raman A, Busby M, Farrugia ME, Ming A, Everett C, Emsley HC, Horvath R, Straub V, Bushby K, Lochmüller H, Chinnery PF, Sarkozy A. Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure. J Neurol Neurosurg Psychiatry. 2014; 85(3):331-8. PMID: 23486992.

853. Nicole S, Chaouch A, Torbergsen T, Bauche S, de Bruyckere E, Fontenille MJ, Horn MA, van Ghelue M, Loseth S, Issop Y, Cox D, Muller JS, Evangelista T, Stalberg E, Ioos C, Barois A, Brochier G, Sternberg D, Fournier E, Hantai D, Abicht A, Dusl M, Laval SH, Griffin H, Eymard B, Lochmüller H. Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy. Brain. 2014; 137(Pt 9):2429-43. PMID: 24951643.

854. *Mora M, Angelini C, Bignami F, Bodin AM, Crimi M, Di Donato JH, Felice A, Jaeger C, Karcagi V, LeCam Y, Lynn S, Meznaric M, Moggio M, Monaco L, Politano L, de la Paz MP, Saker S, Schneiderat P, Ensini M, Garavaglia B, Gurwitz D, Johnson D, Muntoni F, Puymirat J, Reza M, Voit T, Baldo C, Bricarelli FD, Goldwurm S, Merla G, Pegoraro E, Renieri A, Zatloukal K, Filocamo M, Lochmüller H. The EuroBioBank Network: 10 years of hands-on experience of collaborative, transnational biobanking for rare diseases. Eur J Hum Genet. 2014. PMID: 25537360.

855. *Meng J, Chun S, Asfahani R, Lochmüller H, Muntoni F, Morgan J. Human skeletal muscle-derived CD133(+) cells form functional satellite cells after intramuscular transplantation in immunodeficient host mice. Mol Ther. 2014; 22(5):1008-17. PMID: 24569833.

856. Marttila M, Lehtokari VL, Marston S, Nyman TA, Barnerias C, Beggs AH, Bertini E, Ceyhan-Birsoy O, Cintas P, Gerard M, Gilbert-Dussardier B, Hogue JS, Longman C, Eymard B, Frydman M, Kang PB, Klinge L, Kolski H, Lochmüller H, Magy L, Manel V, Mayer M, Mercuri E, North KN, Peudenier-Robert S, Pihko H, Probst FJ, Reisin R, Stewart W, Taratuto AL, de Visser M, Wilichowski E, Winer J, Nowak K, Laing NG, Winder TL, Monnier N, Clarke NF, Pelin K, Gronholm M, Wallgren-Pettersson C. Mutation update and genotype-phenotype correlations of novel and previously described mutations in TPM2 and TPM3 causing congenital myopathies. Hum Mutat. 2014; 35(7):779-90. PMID: 24692096.

857. Lochmüller H, Bushby K. Becker and Duchenne muscular dystrophy: a two-way information process for therapies. J Neurol Neurosurg Psychiatry. 2014; 85(1):5-6. PMID: 23695496.

858. Landfeldt E, Lindgren P, Bell CF, Schmitt C, Guglieri M, Straub V, Lochmüller H, Bushby K. The burden of Duchenne muscular dystrophy: an international, cross-sectional study. Neurology. 2014; 83(6):529-36. PMID: 24991029.

859. Hicks D, Farsani GT, Laval S, Collins J, Sarkozy A, Martoni E, Shah A, Zou Y, Koch M, Bonnemann CG, Roberts M, Lochmüller H, Bushby K, Straub V. Mutations in the collagen

83 | P a g e XII gene define a new form of extracellular matrix-related myopathy. Hum Mol Genet. 2014; 23(9):2353-63. PMID: 24334769.

860. Herrmann DN, Horvath R, Sowden JE, Gonzales M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmüller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S. Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. Am J Hum Genet. 2014; 95(3):332-9. PMID: 25192047.

861. Haberlova J, Mitrovic Z, Zarkovic K, Lovric D, Baric V, Berlengi L, Bilic K, Fumic K, Kranz K, Huebner A, von der Hagen M, Barresi R, Bushby K, Straub V, Baric I, Lochmüller H. Psycho-organic symptoms as early manifestation of adult onset POMT1-related limb girdle muscular dystrophy. Neuromuscul Disord. 2014; 24(11):990-2. PMID: 25088310.

862. Greer KL, Lochmüller H, Flanigan K, Fletcher S, Wilton SD. Targeted exon skipping to correct exon duplications in the dystrophin gene. Mol Ther Nucleic Acids. 2014; 3e155. PMID: 24643206.

863. Gallenmuller C, Muller-Felber W, Dusl M, Stucka R, Guergueltcheva V, Blaschek A, von der Hagen M, Huebner A, Muller JS, Lochmüller H, Abicht A. Salbutamol-responsive limb-girdle congenital myasthenic syndrome due to a novel missense mutation and heteroallelic deletion in MUSK. Neuromuscul Disord. 2014; 24(1):31-5. PMID: 24183479.

864. Dilena R, Abicht A, Sergi P, Comi GP, Di Fonzo A, Chidini G, Natacci F, Barbieri S, Lochmüller H. Congenital myasthenic syndrome due to choline acetyltransferase mutations in infants: clinical suspicion and comprehensive electrophysiological assessment are important for early diagnosis. J Child Neurol. 2014; 29(3):389-93. PMID: 23292760.

865. *De Palma S, Capitanio D, Vasso M, Braghetta P, Scotton C, Bonaldo P, Lochmüller H, Muntoni F, Ferlini A, Gelfi C. Muscle proteomics reveals novel insights into the pathophysiological mechanisms of collagen VI myopathies. J Proteome Res. 2014; 13(11):5022-30. PMID: 25211533.

866. Cynthia Martin F, Hiller M, Spitali P, Oonk S, Dalebout H, Palmblad M, Chaouch A, Guglieri M, Straub V, Lochmüller H, Niks EH, Verschuuren JJ, Aartsma-Rus A, Deelder AM, van der Burgt YE, t Hoen PA. Fibronectin is a serum biomarker for Duchenne muscular dystrophy. Proteomics Clin Appl. 2014; 8(3-4):269-78. PMID: 24458521.

867. Chaouch A, Brennan KM, Hudson J, Longman C, McConville J, Morrison PJ, Farrugia ME, Petty R, Stewart W, Norwood F, Horvath R, Chinnery PF, Costigan D, Winer J, Polvikoski T, Healy E, Sarkozy A, Evangelista T, Pogoryelova O, Eagle M, Bushby K, Straub V, Lochmüller H. Two recurrent mutations are associated with GNE myopathy in the North of Britain. J Neurol Neurosurg Psychiatry. 2014; 85(12):1359-65. PMID: 24695763.

868. Boczonadi V, Muller JS, Pyle A, Munkley J, Dor T, Quartararo J, Ferrero I, Karcagi V, Giunta M, Polvikoski T, Birchall D, Princzinger A, Cinnamon Y, Lutzkendorf S, Piko H, Reza M, Florez L, Santibanez-Koref M, Griffin H, Schuelke M, Elpeleg O, Kalaydjieva L, Lochmüller H, Elliott DJ, Chinnery PF, Edvardson S, Horvath R. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat Commun. 2014; 54287. PMID: 24989451.

869. Bladen CL, Thompson R, Jackson JM, Garland C, Wegel C, Ambrosini A, Pisano P, Walter MC, Schreiber O, Lusakowska A, Jedrzejowska M, Kostera-Pruszczyk A, van der Pol L, Wadman RI, Gredal O, Karaduman A, Topaloglu H, Yilmaz O, Matyushenko V, Rasic VM, Kosac A, Karcagi V, Garami M, Herczegfalvi A, Monges S, Moresco A, Chertkoff L, Chamova T, Guergueltcheva V, Butoianu N, Craiu D, Korngut L, Campbell C, Haberlova J, Strenkova J, Alejandro M, Jimenez A, Ortiz GG, Enriquez GV, Rodrigues M, Roxburgh R,

84 | P a g e Dawkins H, Youngs L, Lahdetie J, Angelkova N, Saugier-Veber P, Cuisset JM, Bloetzer C, Jeannet PY, Klein A, Nascimento A, Tizzano E, Salgado D, Mercuri E, Sejersen T, Kirschner J, Rafferty K, Straub V, Bushby K, Verschuuren J, Beroud C, Lochmüller H. Mapping the differences in care for 5,000 spinal muscular atrophy patients, a survey of 24 national registries in North America, Australasia and Europe. J Neurol. 2014; 261(1):152-63. PMID: 24162038.

870. Balreira A, Boczonadi V, Barca E, Pyle A, Bansagi B, Appleton M, Graham C, Hargreaves IP, Rasic VM, Lochmüller H, Griffin H, Taylor RW, Naini A, Chinnery PF, Hirano M, Quinzii CM, Horvath R. ANO10 mutations cause ataxia and coenzyme Q(1)(0) deficiency. J Neurol. 2014; 261(11):2192-8. PMID: 25182700.

871. *Ayoglu B, Chaouch A, Lochmüller H, Politano L, Bertini E, Spitali P, Hiller M, Niks EH, Gualandi F, Ponten F, Bushby K, Aartsma-Rus A, Schwartz E, Le Priol Y, Straub V, Uhlen M, Cirak S, t Hoen PA, Muntoni F, Ferlini A, Schwenk JM, Nilsson P, Al-Khalili Szigyarto C. Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies. EMBO Mol Med. 2014; 6(7):918-36. PMID: 24920607.

872. Zech M, Lam DD, Francescatto L, Schormair B, Salminen AV, Jochim A, Wieland T, Lichtner P, Peters A, Gieger C, Lochmüller H, Strom TM, Haslinger B, Katsanis N, Winkelmann J. Recessive Mutations in the alpha3 (VI) Collagen Gene COL6A3 Cause Early-Onset Isolated Dystonia. Am J Hum Genet. 2015; 96(6):883-93. PMID: 26004199.

873. Rodger S, Woods KL, Bladen CL, Stringer A, Vry J, Gramsch K, Kirschner J, Thompson R, Bushby K, Lochmüller H. Adult care for Duchenne muscular dystrophy in the UK. J Neurol. 2015; 262(3):629-41. PMID: 25536903.

874. Landfeldt E, Lindgren P, Bell C, Schmitt C, Guglieri M, Straub V, Lochmüller H, Bushby K. Compliance to Care Guidelines for Duchenne Muscular Dystrophy. J Neuromusc Dis. 2015; 2(1):63-72.

875. *Figueroa-Bonaparte S, Hudson J, Barresi R, Polvikoski T, Williams T, Topf A, Harris E, Hilton-Jones D, Petty R, Willis TA, Longman C, Dougan CF, Parton MJ, Hanna MG, Quinlivan R, Farrugia ME, Guglieri M, Bushby K, Straub V, Lochmüller H, Evangelista T. Mutational spectrum and phenotypic variability of VCP-related neurological disease in the UK. J Neurol Neurosurg Psychiatry. 2015. PMID: 26105173.

876. *Ferlini A, Flanigan KM, Lochmüller H, Muntoni F, t Hoen PA, McNally E. 204th ENMC International Workshop on Biomarkers in Duchenne Muscular Dystrophy 24-26 January 2014, Naarden, The Netherlands. Neuromuscul Disord. 2015; 25(2):184-98. PMID: 25529833.

877. Evangelista T, Bansagi B, Pyle A, Griffin H, Douroudis K, Polvikoski T, Antoniadi T, Bushby K, Straub V, Chinnery PF, Lochmüller H, Horvath R. Phenotypic variability of TRPV4 related neuropathies. Neuromuscul Disord. 2015; 25(6):516-21. PMID: 25900305.

878. Dusl M, Senderek J, Muller JS, Vogel JG, Pertl A, Stucka R, Lochmüller H, David R, Abicht A. A 3'-UTR mutation creates a microRNA target site in the GFPT1 gene of patients with congenital myasthenic syndrome. Hum Mol Genet. 2015; 24(12):3418-26. PMID: 25765662.

879. Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K, Dawkins H, Lamont L, Roy AJ, Chamova T, Guergueltcheva V, Chan S, Korngut L, Campbell C, Dai Y, Wang J, Barisic N, Brabec P, Lahdetie J, Walter MC, Schreiber-Katz O, Karcagi V, Garami M, Viswanathan V, Bayat F, Buccella F, Kimura E, Koeks Z, van den Bergen JC, Rodrigues M, Roxburgh R, Lusakowska A, Kostera-Pruszczyk A, Zimowski J, Santos R, Neagu E, Artemieva S, Rasic VM, Vojinovic D, Posada M, Bloetzer C, Jeannet PY, Joncourt F, Diaz-

85 | P a g e Manera J, Gallardo E, Karaduman AA, Topaloglu H, Sherif RE, Stringer A, Shatillo AV, Martin AS, Peay HL, Bellgard MI, Kirschner J, Flanigan KM, Straub V, Bushby K, Verschuuren J, Aartsma-Rus A, Beroud C, Lochmüller H. The TREAT-NMD DMD Global database: Analysis of More Than 7000 Duchenne Muscular Dystrophy Mutations. Hum Mutat. 2015; 36(4):395-402. PMID: 25604253.

880. *Belaya K, Rodriguez Cruz PM, Liu WW, Maxwell S, McGowan S, Farrugia ME, Petty R, Walls TJ, Sedghi M, Basiri K, Yue WW, Sarkozy A, Bertoli M, Pitt M, Kennett R, Schaefer A, Bushby K, Parton M, Lochmüller H, Palace J, Muntoni F, Beeson D. Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies. Brain. 2015. PMID: 26133662.

881. Bansagi B, Antoniadi T, Burton-Jones S, Murphy SM, McHugh J, Alexander M, Wells R, Davies J, Hilton-Jones D, Lochmüller H, Chinnery P, Horvath R. Genotype/phenotype correlations in AARS-related neuropathy in a cohort of patients from the United Kingdom and Ireland. J Neurol. 2015. PMID: 26032230.

882. Vissing J, Barresi R, Witting N, Van Ghelue M, Gammelgaard L, Bindoff LA, Straub V, Lochmüller H, Hudson J, Wahl CM, Arnardottir S, Dahlbom K, Jonsrud C, Duno M. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy. Brain. 2016. PMID: 27259757

883. *Scotton C, Bovolenta M, Schwartz E, Falzarano MS, Martoni E, Passarelli C, Armaroli A, Osman H, Rodolico C, Messina S, Pegoraro E, D'Amico A, Bertini E, Gualandi F, Neri M, Selvatici R, Boffi P, Maioli MA, Lochmüller H, Straub V, Bushby K, Castrignano T, Pesole G, Sabatelli P, Merlini L, Braghetta P, Bonaldo P, Bernardi P, Foley R, Cirak S, Zaharieva I, Muntoni F, Capitanio D, Gelfi C, Kotelnikova E, Yuryev A, Lebowitz M, Zhang X, Hodge BA, Esser KA, Ferlini A. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy. J Cell Sci. 2016;129:1671-1684. PMID: 26945058

884. *Rodriguez Cruz PM, Belaya K, Basiri K, Sedghi M, Farrugia ME, Holton JL, Liu WW, Maxwell S, Petty R, Walls TJ, Kennett R, Pitt M, Sarkozy A, Parton M, Lochmüller H, Muntoni F, Palace J, Beeson D. Clinical features of the myasthenic syndrome arising from mutations in GMPPB. J Neurol Neurosurg Psychiatry. 2016. PMID: 27147698

885. Oonk S, Spitali P, Hiller M, Switzar L, Dalebout H, Calissano M, Lochmüller H, Aartsma-Rus A, Hoen PA, van der Burgt YE. Comparative mass spectrometric and immunoassay-based proteome analysis in serum of Duchenne muscular dystrophy patients. Proteomics Clin Appl. 2016;10:290-299. PMID: 26680509

886. O'Connor E, Topf A, Muller JS, Cox D, Evangelista T, Colomer J, Abicht A, Senderek J, Hasselmann O, Yaramis A, Laval SH, Lochmüller H. Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome. Brain. 2016. PMID: 27259756

887. Natera-de Benito D, Nascimento A, Abicht A, Ortez C, Jou C, Muller JS, Evangelista T, Topf A, Thompson R, Jimenez-Mallebrera C, Colomer J, Lochmüller H. KLHL40-related nemaline myopathy with a sustained, positive response to treatment with acetylcholinesterase inhibitors. J Neurol. 2016;263:517-523. PMID: 26754003

888. *Meng J, Counsell JR, Reza M, Laval SH, Danos O, Thrasher A, Lochmüller H, Muntoni F, Morgan JE. Autologous skeletal muscle derived cells expressing a novel functional dystrophin provide a potential therapy for Duchenne Muscular Dystrophy. Sci Rep. 2016;6:19750. PMID: 26813695

86 | P a g e 889. McCormack P, Kole A, Gainotti S, Mascalzoni D, Molster C, Lochmüller H, Woods S. 'You should at least ask'. The expectations, hopes and fears of rare disease patients on large-scale data and biomaterial sharing for genomics research. Eur J Hum Genet. 2016. PMID: 27049302

890. Landfeldt E, Mayhew A, Eagle M, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, Bushby K. Corrigendum to "Development and psychometric analysis of the Duchenne muscular dystrophy Functional Ability Self-Assessment Tool (DMDSAT)" [Neuromuscular Disorders 25 (2015) 937-944]. Neuromuscul Disord. 2016;26:329. PMID: 27087611

891. Landfeldt E, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, Bushby K. Health-related quality of life in patients with Duchenne muscular dystrophy: a multinational, cross-sectional study. Dev Med Child Neurol. 2016;58:508-515. PMID: 26483095

892. Landfeldt E, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, Bushby K. Quantifying the burden of caregiving in Duchenne muscular dystrophy. J Neurol. 2016;263:906-915. PMID: 26964543

893. Khan MM, Lustrino D, Silveira WA, Wild F, Straka T, Issop Y, O'Connor E, Cox D, Reischl M, Marquardt T, Labeit D, Labeit S, Benoit E, Molgo J, Lochmüller H, Witzemann V, Kettelhut IC, Navegantes LC, Pozzan T, Rudolf R. Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease. Proc Natl Acad Sci U S A. 2016;113:746-750. PMID: 26733679

894. *Figueroa-Bonaparte S, Hudson J, Barresi R, Polvikoski T, Williams T, Topf A, Harris E, Hilton-Jones D, Petty R, Willis TA, Longman C, Dougan CF, Parton MJ, Hanna MG, Quinlivan R, Farrugia ME, Guglieri M, Bushby K, Straub V, Lochmüller H, Evangelista T. Mutational spectrum and phenotypic variability of VCP-related neurological disease in the UK. J Neurol Neurosurg Psychiatry. 2016;87:680-681. PMID: 26105173

895. Evangelista T, Wood L, Fernandez-Torron R, Williams M, Smith D, Lunt P, Hudson J, Norwood F, Orrell R, Willis T, Hilton-Jones D, Rafferty K, Guglieri M, Lochmüller H. Design, set-up and utility of the UK facioscapulohumeral muscular dystrophy patient registry. J Neurol. 2016;263:1401-1408. PMID: 27159994

896. Evangelista T, Weihl CC, Kimonis V, Lochmüller H, Consortium VCPrd. 215th ENMC International Workshop VCP-related multi-system proteinopathy (IBMPFD) 13-15 November 2015, Heemskerk, The Netherlands. Neuromuscul Disord. 2016. PMID: 27312024

Robert McFarland

897. Oláhová M, Haack TB, Alston CL, Houghton JA, He L, Morris AA, Brown GK, McFarland R, Chrzanowska-Lightowlers ZM, Lightowlers RN, Prokisch H, Taylor RW.A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency. Eur J Hum Genet. 2014 Oct 8. PMID: 25293719

898. Hall AM, Vilasi A, Garcia-Perez I, Lapsley M, Alston CL, Pitceathly RD, McFarland R, Schaefer AM, Turnbull DM, Beaumont NJ, Hsuan JJ, Cutillas PR, Lindon JC, Holmes E, Unwin RJ, Taylor RW, Gorman GS, Rahman S, Hanna MG. The urinary proteome and metabonome differ from normal in adults with mitochondrial disease. Kidney Int. 2014 Sep 10. IF 8.52. PMID: 25027879

899. Pitceathly RD, McFarland R. Mitochondrial myopathies in adults and children: management and therapy development. Curr Opin Neurol. 2014 Oct;27(5):576-82. IF 5.73. PMID: 25027879

87 | P a g e 900. Oláhová M, Hardy SA, Hall J, Yarham JW, Haack TB, Wilson WC, Alston CL, He L, Aznauryan E, Brown RM, Brown GK, Morris AA, Mundy H, Broomfield A, Barbosa IA, Simpson MA, Deshpande C, Moeslinger D, Koch J, Stettner GM, Bonnen PE, Prokisch H, Lightowlers RN, McFarland R, Chrzanowska-Lightowlers ZM, Taylor RW. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French- Canadian population. Brain. 2015 Dec;138(Pt 12):3503-19. IF 10.4. PMID: 26510951

901. Whittaker RG, Devine HE, Gorman GS, Schaefer AM, Horvath R, Ng Y, Nesbitt V, Lax NZ, McFarland R, Cunningham MO, Taylor RW, Turnbull DM. Epilepsy in adults with mitochondrial disease: A cohort study. Ann Neurol. 2015 Dec;78(6):949-57. IF 9.98. PMID: 26381753

902. Barends M, Verschuren L, Morava E, Nesbitt V, Turnbull D, McFarland R. Causes of Death in Adults with Mitochondrial Disease. JIMD Rep. 2015 Sep 10. [Epub ahead of print] PMID: 26354038

903. Ng YS, Grady JP, Lax NZ, Bourke JP, Alston CL, Hardy SA, Falkous G, Schaefer AG, Radunovic A, Mohiddin SA, Ralph M, Alhakim A, Taylor RW, McFarland R, Turnbull DM, Gorman GS. Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults. Eur Heart J. 2015 Jul 17. pii: ehv306. [Epub ahead of print] IF 15.20. PMID: 26188002

904. Lax NZ, Alston CL, Schon K, Park SM, Krishnakumar D, He L, Falkous G, Ogilvy-Stuart A, Lees C, King RH, Hargreaves IP, Brown GK, McFarland R, Dean AF, Taylor RW. Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations. J Neuropathol Exp Neurol. 2015 Jul;74(7):688-703 IF 4.37. PMID: 26083569

905. Gorman GS, Elson JL, Newman J, Payne B, McFarland R, Newton JL, Turnbull DM. Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease. Neuromuscul Disord. 2015 Jul;25(7):563-6. Epub 2015 Apr 23. IF 3.13. PMID: 26031904

906. Alston CL, Berti CC, Blakely EL, Oláhová M, He L, McMahon CJ, Olpin SE, Hargreaves IP, Nolli C, McFarland R, Goffrini P, O'Sullivan MJ, Taylor RW. A recessive homozygous p.Asp92Gly SDHD mutation causes prenatal cardiomyopathy and a severe mitochondrial complex II deficiency. Hum Genet. 2015 May 26. [Epub ahead of print] IF 5.07. PMID: 26008905

907. Huemer M, Karall D, Schossig A, Abdenur JE, Al Jasmi F, Biagosch C, Distelmaier F, Freisinger P, Graham BH, Haack TB, Hauser N, Hertecant J, Ebrahimi-Fakhari D, Konstantopoulou V, Leydiker K, Lourenco CM, Scholl-Bürgi S, Wilichowski E, Wolf NI, Wortmann SB, Taylor RW, Mayr JA, Bonnen PE, Sperl W, Prokisch H, McFarland R. Clinical, morphological, biochemical, imaging and outcome parameters in 21 individuals with mitochondrial maintenance defect related to FBXL4 mutations.J Inherit Metab Dis. 2015 Apr 14 IF 4.14. PMID: 25868664

908. Brito S, Thompson K, Campistol J, Colomer J, Hardy SA, He L, Fernández-Marmiesse A, Palacios L, Jou C, Jiménez-Mallebrera C, Armstrong J, Montero R, Artuch R, Tischner C, Wenz T, McFarland R, Taylor RW. Long-term survival in a child with severe encephalopathy, multiple respiratory chain deficiency and GFM1 mutations. Front Genet. 2015 Mar 23;6:102. IF N/A*Besse A, Wu P, Bruni F, Donti T, Graham BH, Craigen WJ, McFarland R, Moretti P, Lalani S, Scott KL, Taylor RW, Bonnen PE. The GABA Transaminase, ABAT, Is Essential for Mitochondrial Nucleoside Metabolism. Cell Metab. 2015 Mar 3;21(3):417-27. IF 17.88. PMID: 25738457

88 | P a g e 909. Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, Taylor RW, Turnbull DM, McFarland R. Prevalence of nuclear and mtDNA mutations related to adult mitochondrial disease. Ann Neurol. 2015 May;77(5):753-9. IF 11.91. PMID: 25652200

910. Gorman GS, Grady JP, Ng Y, Schaefer AM, McNally RJ, Chinnery PF, Yu-Wai-Man P, Herbert M, Taylor RW, McFarland R, Turnbull DM. Mitochondrial Donation - How Many Women Could Benefit? N Engl J Med. 2015 Feb 26;372(9):885-7. IF 54.42 PMID: 25629662

911. Gorman GS, Blakely EL, Hornig-Do HT, Tuppen HA, Greaves LC, He L, Baker A, Falkous G, Newman J, Trenell MI, Lecky B, Petty RK, Turnbull DM, McFarland R, Taylor RW. Novel MTND1 mutations cause isolated exercise intolerance, complex I deficiency and increased assembly factor expression. Clin Sci (Lond). 2015 Jan 27. IF 5.63. PMID: 25626417

912. Gorman GS, Pfeffer G, Griffin H, Blakely EL, Kurzawa-Akanbi M, Gabriel J, Sitarz K, Roberts M, Schoser B, Pyle A, Schaefer AM, McFarland R, Turnbull DM, Horvath R, Chinnery PF, Taylor RW. Clonal expansion of secondary mitochondrial DNA deletions associated with spinocerebellar ataxia type 28. JAMA Neurol. 2015 Jan 1;72(1):106-11. IF 7.0. PMID: 25420100

913. Ng YS, Feeney C, Schaefer AM, Holmes CE, Hynd P, Alston CL, Grady JP, Roberts M, Maguire M, Bright A, Taylor RW, Yiannakou Y, McFarland R, Turnbull DM, Gorman GS. Pseudo-obstruction, stroke and mitochondrial dysfunction: A lethal combination. Ann Neurol. 2016 Jul 25. PMID: 27453452

914. Sallevelt SC, de Die-Smulders CE, Hendrickx AT, Hellebrekers DM, de Coo IF, Alston CL, Knowles C, Taylor RW, McFarland R, Smeets HJ. De novo mtDNA point mutations are common and have a low recurrence risk.J Med Genet. 2016 Jul 22. PMID: 26312584

915. Ng YS, Alston CL, Diodato D, Morris AA, Ulrick N, Kmoch S, Houštěk J, Martinelli D, Haghighi A, Atiq M, Gamero MA, Garcia-Martinez E, Kratochvílová H, Santra S, Brown RM, Brown GK, Ragge N, Monavari A, Pysden K, Ravn K, Casey JP, Khan A, Chakrapani A, Vassallo G, Simons C, McKeever K, O'Sullivan S, Childs AM, Østergaard E, Vanderver A, Goldstein A, Vogt J, Taylor RW, McFarland R. The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease. J Med Genet. 2016 Jul 13. PMID: 27412952

916. Metodiev MD, Thompson K, Alston CL, Morris AA, He L, Assouline Z, Rio M, Bahi- Buisson N, Pyle A, Griffin H, Siira S, Filipovska A, Munnich A, Chinnery PF, McFarland R, Rötig A, Taylor RW. Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies. Am J Hum Genet. 2016 Jul 7;99(1):246. PMID: 27392079

917. Gupta A, Colmenero I, Ragge NK, Blakely EL, He L, McFarland R, Taylor RW, Vogt J, Milford DV. Compound heterozygous RMND1 gene variants associated with chronic kidney disease, dilated cardiomyopathy and neurological involvement: a case report. BMC Res Notes. 2016 Jun 27;9(1):325. PMID: 27350610

918. Koene S, Hendriks JC, Dirks I, de Boer L, de Vries MC, Janssen MC, Smuts I, Fung CW, Wong VC, de Coo IR, Vill K, Stendel C, Klopstock T, Falk MJ, McCormick EM, McFarland R, de Groot IJ, Smeitink JA. International Paediatric Mitochondrial Disease Scale. J Inherit Metab Dis. 2016 Jun 9. IF 3.81 PMID: 27277220

919. Metodiev MD, Thompson K, Alston CL, Morris AA, He L, Assouline Z, Rio M, Bahi- Buisson N, Pyle A, Griffin H, Siira S, Filipovska A, Munnich A, Chinnery PF, McFarland R, Rötig A, Taylor RW. Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA

89 | P a g e Processing and Multiple Respiratory Chain Deficiencies. Am J Hum Genet. 2016 May 5;98(5):993-1000. IF 10.93. PMID: 27132592

920. Martikainen MH, Ng YS, Gorman GS, Alston CL, Blakely EL, Schaefer AM, Chinnery PF, Burn DJ, Taylor RW, McFarland R, Turnbull DM. Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease. JAMA Neurol. 2016 Jun 1;73(6):668-74. IF 7.42. PMID: 27111573

921. Alston CL, Howard C, Oláhová M, Hardy SA, He L, Murray PG, O'Sullivan S, Doherty G, Shield JP, Hargreaves IP, Monavari AA, Knerr I, McCarthy P, Morris AA, Thorburn DR, Prokisch H, Clayton PE, McFarland R, Hughes J, Crushell E, Taylor RW. A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype. J Med Genet. 2016 Apr 18. IF 5.65. PMID: 27091925

922. Kullar PJ, Quail J, Lindsey P, Wilson JA, Horvath R, Yu-Wai-Man P, Gorman GS, Taylor RW, Ng Y, McFarland R, Moore BC, Chinnery PF. Both mitochondrial DNA and mitonuclear gene mutations cause hearing loss through cochlear dysfunction. Brain. 2016 Jun;139(Pt 6):e33. IF 10.4. PMID: 27016405

923. Carrozzo R, Verrigni D, Rasmussen M, de Coo R, Amartino H, Bianchi M, Buhas D, Mesli S, Naess K, Born AP, Woldseth B, Prontera P, Batbayli M, Ravn K, Joensen F, Cordelli DM, Santorelli FM, Tulinius M, Darin N, Duno M, Jouvencel P, Burlina A, Stangoni G, Bertini E, Redonnet-Vernhet I, Wibrand F, Dionisi-Vici C, Uusimaa J, Vieira P, Osorio AN, McFarland R, Taylor RW, Holme E, Ostergaard E. Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1: phenotype and genotype correlations in 71 patients. J Inherit Metab Dis. 2016 Mar;39(2):243-52 IF 3.81. PMID: 26475597

James Miller

924. Rose MR; ENMC IBM Working Group. 188th ENMC International Workshop: Inclusion Body Myositis, 2-4 December 2011, Naarden, The Netherlands. Neuromuscul Disord. 2013 Dec;23(12):1044-55. PMID: 24268584

925. Rygiel KA, Miller J, Grady JP, Rocha MC, Taylor RW, Turnbull DM. Mitochondrial and inflammatory changes in sporadic Inclusion Body Myositis. Neuropathol Appl Neurobiol. 2014 Apr 18. PMID: 24750247

926. Rodríguez Cruz PM, Luo YB, Miller J, Junckerstorff RC, Mastaglia FL, Fabian V. An analysis of the sensitivity and specificity of MHC-I and MHC-II immunohistochemical staining in muscle biopsies for the diagnosis of inflammatory myopathies. Neuromuscul Disord. 2014 Jun 30. PMID: 25153265

927. Whittaker RG, Chinnery PF, Miller JA Teaching video neuroimages: muscle cramps and a raised creatine kinase. Neurology. 2014 Jun 17;82(24):e220-1. PMID: 24960836

928. Rose MR, Jones K, Leong K, Walter MC, Miller J, Dalakas MC, Brassington R, Griggs R. Treatment for inclusion body myositis. Cochrane Database of Systematic Reviews 2015, Issue 6. Art. No.: CD001555. DOI: 10.1002/14651858.CD001555

929. Zhao S, Mutch K, Elsone L, Miller J, Jacob A. An unusual case of 'itchy paralysis': neuromyelitis optica presenting with severe neuropathic itch. Pract Neurol. 2015 Apr;15(2):149-51. PubMed PMID: 25404417.

90 | P a g e 930. Boglarka Bansagi, Helen Griffin, Roger Whittaker, Thalia Antoniadi, James Miller, Teresinha Evangelista, Sarah Burton-Jones, Jennifer Duff, Stephanie Kleinle, Hannah Steele Anna Bradshaw, Venkatateswaran Ramesh, Edit Franko, Angela Pyle, Veronika Boczonadi, Hanns Lochmüller, Patrick F. Chinnery, Rita Horvath. Genes and disease mechanisms in 105 patients with hereditary motor neuropathies from the North of England. Ann Neurol. 2016. In press.

Volker Straub

931. *Zaharieva IT, Calissano M, Scoto M, Preston M, Cirak S, Feng L, Collins J, Kole R, Guglieri M, Straub V, Bushby K, Ferlini A, Morgan JE, Muntoni F. Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne muscular Dystrophy. PLoS One. 2013; 8(11):e80263. PMID: 24282529

932. *Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmüller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PLoS One. 2013; 8(8):e70993. PMID: 23967145

933. Wagner M, Chaouch A, Muller JS, Polvikoski T, Willis TA, Sarkozy A, Eagle M, Bushby K, Straub V, Lochmüller H. Presymptomatic late-onset Pompe disease identified by the dried blood spot test. Neuromuscul Disord. 2013; 23(1):89-92. PMID: 23062590

934. Vissing J, Lukacs Z, Straub V. Diagnosis of Pompe disease: muscle biopsy vs blood- based assays. JAMA Neurol. 2013; 70(7):923-7. PMID: 23649721

935. *Sarkozy A, Hicks D, Hudson J, Laval SH, Barresi R, Hilton-Jones D, Deschauer M, Harris E, Rufibach L, Hwang E, Bashir R, Walter MC, Krause S, van den Bergh P, Illa I, Penisson-Besnier I, De Waele L, Turnbull D, Guglieri M, Schrank B, Schoser B, Seeger J, Schreiber H, Glaser D, Eagle M, Bailey G, Walters R, Longman C, Norwood F, Winer J, Muntoni F, Hanna M, Roberts M, Bindoff LA, Brierley C, Cooper RG, Cottrell DA, Davies NP, Gibson A, Gorman GS, Hammans S, Jackson AP, Khan A, Lane R, McConville J, McEntagart M, Al-Memar A, Nixon J, Panicker J, Parton M, Petty R, Price CJ, Rakowicz W, Ray P, Schapira AH, Swingler R, Turner C, Wagner KR, Maddison P, Shaw PJ, Straub V, Bushby K, Lochmüller H. ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation. Hum Mutat. 2013; 34(8):1111-8. PMID: 23606453

936. Rodger S, Lochmüller H, Tassoni A, Gramsch K, Konig K, Bushby K, Straub V, Korinthenberg R, Kirschner J. The TREAT-NMD care and trial site registry: an online registry to facilitate clinical research for neuromuscular diseases. Orphanet J Rare Dis. 2013; 8171. PMID: 24148153

937. *Quinlivan R, Mitsuahashi S, Sewry C, Cirak S, Aoyama C, Mooore D, Abbs S, Robb S, Newton T, Moss C, Birchall D, Sugimoto H, Bushby K, Guglieri M, Muntoni F, Nishino I, Straub V. Muscular dystrophy with large mitochondria associated with mutations in the CHKB gene in three British patients: extending the clinical and pathological phenotype. Neuromuscul Disord. 2013; 23(7):549-56. PMID: 23692895

938. Pfeffer G, Barresi R, Wilson IJ, Hardy SA, Griffin H, Hudson J, Elliott HR, Ramesh AV, Radunovic A, Winer J, Vaidya S, Raman A, Busby M, Farrugia ME, Ming A, Everett C, Emsley HCA, Horvath R, Straub V, Bushby K, Lochmüller H, Chinnery P, Sarkozy A. A founder mutation in the titin gene is a common cause of myofibrillar myopathy with early respiratory failure. Neuromuscular Disorders. 2013; 23(9-10):820-. PMID: 23486992

91 | P a g e 939. Muller T, Mizumoto S, Suresh I, Komatsu Y, Vodopiutz J, Dundar M, Straub V, Lingenhel A, Melmer A, Lechner S, Zschocke J, Sugahara K, Janecke AR. Loss of dermatan sulfate epimerase (DSE) function results in musculocontractural Ehlers-Danlos syndrome. Hum Mol Genet. 2013; 22(18):3761-72. PMID: 23704329

940. *McCormack P, Woods S, Aartsma-Rus A, Hagger L, Herczegfalvi A, Heslop E, Irwin J, Kirschner J, Moeschen P, Muntoni F, Ouillade MC, Rahbek J, Rehmann-Sutter C, Rouault F, Sejersen T, Vroom E, Straub V, Bushby K, Ferlini A. Guidance in social and ethical issues related to clinical, diagnostic care and novel therapies for hereditary neuromuscular rare diseases: "translating" the translational. PLoS Curr. 2013; 5. PMID: 23330068

941. *Loseth S, Voermans NC, Torbergsen T, Lillis S, Jonsrud C, Lindal S, Kamsteeg EJ, Lammens M, Broman M, Dekomien G, Maddison P, Muntoni F, Sewry C, Radunovic A, de Visser M, Straub V, van Engelen B, Jungbluth H. A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. J Neurol. 2013; 260(6):1504-10. PMID: 23329375

942. Hollingsworth KG, Willis TA, Bates MGD, Dixon BJ, Lochmüller H, Bushby K, Bourke J, MacGowan GA, Straub V. Subepicardial dysfunction leads to global left ventricular systolic impairment in patients with limb girdle muscular dystrophy 2I. European Journal of Heart Failure. 2013; 15(9):986-94. PMID: 23576288

943. Hollingsworth KG, Garrood P, Eagle M, Bushby K, Straub V. Magnetic resonance imaging in Duchenne muscular dystrophy: longitudinal assessment of natural history over 18 months. Muscle Nerve. 2013; 48(4):586-8. PMID: 23620230

944. Harris E, Laval S, Hudson J, Barresi R, De Waele L, Straub V, Lochmüller H, Bushby K, Sarkozy A. Undiagnosed genetic muscle disease in the north of England: an in depth phenotype analysis. PLoS Curr. 2013; 5. PMID: 23788081

945. Greally E, Davison BJ, Blain A, Laval S, Blamire A, Straub V, MacGowan GA. Heterogeneous abnormalities of in-vivo left ventricular calcium influx and function in mouse models of muscular dystrophy cardiomyopathy. J Cardiovasc Magn Reson. 2013; 154. PMID: 23324314

946. *Foley AR, Quijano-Roy S, Collins J, Straub V, McCallum M, Deconinck N, Mercuri E, Pane M, D'Amico A, Bertini E, North K, Ryan MM, Richard P, Allamand V, Hicks D, Lamande S, Hu Y, Gualandi F, Auh S, Muntoni F, Bonnemann CG. Natural history of pulmonary function in collagen VI-related myopathies. Brain. 2013; 136(Pt 12):3625-33. PMID: 24271325

947. *Dlamini N, Voermans NC, Lillis S, Stewart K, Kamsteeg EJ, Drost G, Quinlivan R, Snoeck M, Norwood F, Radunovic A, Straub V, Roberts M, Vrancken AF, van der Pol WL, de Coo RI, Manzur AY, Yau S, Abbs S, King A, Lammens M, Hopkins PM, Mohammed S, Treves S, Muntoni F, Wraige E, Davis MR, van Engelen B, Jungbluth H. Mutations in RYR1 are a common cause of exertional myalgia and rhabdomyolysis. Neuromuscul Disord. 2013; 23(7):540-8. PMID: 23628358

948. Cooke RM, Mistry R, Challiss RA, Straub VA. Nitric oxide synthesis and cGMP production is important for neurite growth and remodeling after axotomy. J Neurosci. 2013; 33(13):5626-37. PMID: 23536077

92 | P a g e 949. Blain A, Greally E, Laval S, Blamire A, Straub V, MacGowan GA. Beta-blockers, left and right ventricular function, and in-vivo calcium influx in muscular dystrophy cardiomyopathy. PLoS One. 2013; 8(2):e57260. PMID: 23437355

950. Bladen CL, Rafferty K, Straub V, Monges S, Moresco A, Dawkins H, Roy A, Chamova T, Guergueltcheva V, Korngut L, Campbell C, Dai Y, Barisic N, Kos T, Brabec P, Rahbek J, Lahdetie J, Tuffery-Giraud S, Claustres M, Leturcq F, Ben Yaou R, Walter MC, Schreiber O, Karcagi V, Herczegfalvi A, Viswanathan V, Bayat F, de la Caridad Guerrero Sarmiento I, Ambrosini A, Ceradini F, Kimura E, van den Bergen JC, Rodrigues M, Roxburgh R, Lusakowska A, Oliveira J, Santos R, Neagu E, Butoianu N, Artemieva S, Rasic VM, Posada M, Palau F, Lindvall B, Bloetzer C, Karaduman A, Topaloglu H, Inal S, Oflazer P, Stringer A, Shatillo AV, Martin AS, Peay H, Flanigan KM, Salgado D, von Rekowski B, Lynn S, Heslop E, Gainotti S, Taruscio D, Kirschner J, Verschuuren J, Bushby K, Beroud C, Lochmüller H. The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia. Hum Mutat. 2013; 34(11):1449-57. PMID: 23913485

951. Zou Y, Zwolanek D, Izu Y, Gandhy S, Schreiber G, Brockmann K, Devoto M, Tian Z, Hu Y, Veit G, Meier M, Stetefeld J, Hicks D, Straub V, Voermans NC, Birk DE, Barton ER, Koch M, Bonnemann CG. Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice. Hum Mol Genet. 2014; 23(9):2339- 52. PMID: 24334604

952.*Willis TA, Hollingsworth KG, Coombs A, Sveen ML, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CD, Thornton JS, Bushby K, Lochmüller H, Hanna MG, Hogrel JY, Carlier PG, Vissing J, Straub V. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross- sectional study. PLoS One. 2014; 9(2):e90377. PMID: 24587344

953. *Voit T, Topaloglu H, Straub V, Muntoni F, Deconinck N, Campion G, De Kimpe SJ, Eagle M, Guglieri M, Hood S, Liefaard L, Lourbakos A, Morgan A, Nakielny J, Quarcoo N, Ricotti V, Rolfe K, Servais L, Wardell C, Wilson R, Wright P, Kraus JE. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol. 2014; 13(10):987-96. PMID: 25209738

954. Van Ruiten HJ, Straub V, Bushby K, Guglieri M. Improving recognition of Duchenne muscular dystrophy: a retrospective case note review. Arch Dis Child. 2014; 99(12):1074-7. PMID: 25187493

955. *Van den Bergen JC, Hiller M, Bohringer S, Vijfhuizen L, Ginjaar HB, Chaouch A, Bushby K, Straub V, Scoto M, Cirak S, Humbertclaude V, Claustres M, Scotton C, Passarelli C, Lochmüller H, Muntoni F, Tuffery-Giraud S, Ferlini A, Aartsma-Rus AM, Verschuuren JJ, t Hoen PA, Spitali P. Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants. J Neurol Neurosurg Psychiatry. 2014. PMID: 25476005

956. Rutschow D, Bauer R, Gohringer C, Bekeredjian R, Schinkel S, Straub V, Koenen M, Weichenhan D, Katus HA, Muller OJ. S151A delta-sarcoglycan mutation causes a mild phenotype of cardiomyopathy in mice. Eur J Hum Genet. 2014; 22(1):119-25. PMID: 23695275

957. Pfeffer G, Barresi R, Wilson IJ, Hardy SA, Griffin H, Hudson J, Elliott HR, Ramesh AV, Radunovic A, Winer JB, Vaidya S, Raman A, Busby M, Farrugia ME, Ming A, Everett C, Emsley HC, Horvath R, Straub V, Bushby K, Lochmüller H, Chinnery PF, Sarkozy A.

93 | P a g e Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure. J Neurol Neurosurg Psychiatry. 2014; 85(3):331-8. PMID: 23486992

958. Landfeldt E, Lindgren P, Bell CF, Schmitt C, Guglieri M, Straub V, Lochmüller H, Bushby K. The burden of Duchenne muscular dystrophy: an international, cross-sectional study. Neurology. 2014; 83(6):529-36. PMID: 24991029

959. Lamont PJ, Wallefeld W, Hilton-Jones D, Udd B, Argov Z, Barboi AC, Bonneman C, Boycott KM, Bushby K, Connolly AM, Davies N, Beggs AH, Cox GF, Dastgir J, DeChene ET, Gooding R, Jungbluth H, Muelas N, Palmio J, Penttila S, Schmedding E, Suominen T, Straub V, Staples C, Van den Bergh PY, Vilchez JJ, Wagner KR, Wheeler PG, Wraige E, Laing NG. Novel Mutations Widen the Phenotypic Spectrum of Slow Skeletal/beta-Cardiac Myosin (MYH7) Distal Myopathy. Hum Mutat. 2014; 35(7):868-79. PMID: 24664454

960. Hollingsworth KG, Higgins DM, McCallum M, Ward L, Coombs A, Straub V. Investigating the quantitative fidelity of prospectively undersampled chemical shift imaging in muscular dystrophy with compressed sensing and parallel imaging reconstruction. Magn Reson Med. 2014; 72(6):1610-9. PMID: 24347306

961. Hicks D, Farsani GT, Laval S, Collins J, Sarkozy A, Martoni E, Shah A, Zou Y, Koch M, Bonnemann CG, Roberts M, Lochmüller H, Bushby K, Straub V. Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy. Hum Mol Genet. 2014; 23(9):2353-63. PMID: 24334769

962. Haberlova J, Mitrovic Z, Zarkovic K, Lovric D, Baric V, Berlengi L, Bilic K, Fumic K, Kranz K, Huebner A, von der Hagen M, Barresi R, Bushby K, Straub V, Baric I, Lochmüller H. Psycho-organic symptoms as early manifestation of adult onset POMT1- related limb girdle muscular dystrophy. Neuromuscul Disord. 2014; 24(11):990-2. PMID: 25088310

963. *Foley AR, Menezes MP, Pandraud A, Gonzalez MA, Al-Odaib A, Abrams AJ, Sugano K, Yonezawa A, Manzur AY, Burns J, Hughes I, McCullagh BG, Jungbluth H, Lim MJ, Lin JP, Megarbane A, Urtizberea JA, Shah AH, Antony J, Webster R, Broomfield A, Ng J, Mathew AA, O'Byrne JJ, Forman E, Scoto M, Prasad M, O'Brien K, Olpin S, Oppenheim M, Hargreaves I, Land JM, Wang MX, Carpenter K, Horvath R, Straub V, Lek M, Gold W, Farrell MO, Brandner S, Phadke R, Matsubara K, McGarvey ML, Scherer SS, Baxter PS, King MD, Clayton P, Rahman S, Reilly MM, Ouvrier RA, Christodoulou J, Zuchner S, Muntoni F, Houlden H. Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain. 2014; 137(Pt 1):44-56. PMID: 24253200

964. Cynthia Martin F, Hiller M, Spitali P, Oonk S, Dalebout H, Palmblad M, Chaouch A, Guglieri M, Straub V, Lochmüller H, Niks EH, Verschuuren JJ, Aartsma-Rus A, Deelder AM, van der Burgt YE, t Hoen PA. Fibronectin is a serum biomarker for Duchenne muscular dystrophy. Proteomics Clin Appl. 2014; 8(3-4):269-78. PMID: 24458521

965. Chaouch A, Porcelli V, D. C, Edvardson S, Scarcia P, De Grassi A, Pierri C, Cossins J, Laval S, Griffin H, Mueller J, Evangelista T, Topf A, Abicht A, Huebner A, von der Hagen M, Busbhy K, Straub V, Horvath R, Elpeleg O, Palace J, Senderek J, Beeson D, Palmieri L, Lochmüller H. Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. Journal of Neuromuscular Diseases. 2014; 1(1):75- 90. PMID: 26870663

966. Chaouch A, Brennan KM, Hudson J, Longman C, McConville J, Morrison PJ, Farrugia ME, Petty R, Stewart W, Norwood F, Horvath R, Chinnery PF, Costigan D, Winer J, Polvikoski T, Healy E, Sarkozy A, Evangelista T, Pogoryelova O, Eagle M, Bushby K,

94 | P a g e Straub V, Lochmüller H. Two recurrent mutations are associated with GNE myopathy in the North of Britain. J Neurol Neurosurg Psychiatry. 2014; 85(12):1359-65. PMID: 24695763

967. Laden CL, Thompson R, Jackson JM, Garland C, Wegel C, Ambrosini A, Pisano P, Walter MC, Schreiber O, Lusakowska A, Jedrzejowska M, Kostera-Pruszczyk A, van der Pol L, Wadman RI, Gredal O, Karaduman A, Topaloglu H, Yilmaz O, Matyushenko V, Rasic VM, Kosac A, Karcagi V, Garami M, Herczegfalvi A, Monges S, Moresco A, Chertkoff L, Chamova T, Guergueltcheva V, Butoianu N, Craiu D, Korngut L, Campbell C, Haberlova J, Strenkova J, Alejandro M, Jimenez A, Ortiz GG, Enriquez GV, Rodrigues M, Roxburgh R, Dawkins H, Youngs L, Lahdetie J, Angelkova N, Saugier-Veber P, Cuisset JM, Bloetzer C, Jeannet PY, Klein A, Nascimento A, Tizzano E, Salgado D, Mercuri E, Sejersen T, Kirschner J, Rafferty K, Straub V, Bushby K, Verschuuren J, Beroud C, Lochmüller H. Mapping the differences in care for 5,000 spinal muscular atrophy patients, a survey of 24 national registries in North America, Australasia and Europe. J Neurol. 2014; 261(1):152-63. PMID: 24162038

968. *Ayoglu B, Chaouch A, Lochmüller H, Politano L, Bertini E, Spitali P, Hiller M, Niks EH, Gualandi F, Ponten F, Bushby K, Aartsma-Rus A, Schwartz E, Le Priol Y, Straub V, Uhlen M, Cirak S, t Hoen PA, Muntoni F, Ferlini A, Schwenk JM, Nilsson P, Al-Khalili Szigyarto C. Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies. EMBO Mol Med. 2014; 6(7):918-36. PMID: 24920607

969. *Anthony K, Arechavala-Gomeza V, Taylor LE, Vulin A, Kaminoh Y, Torelli S, Feng L, Janghra N, Bonne G, Beuvin M, Barresi R, Henderson M, Laval S, Lourbakos A, Campion G, Straub V, Voit T, Sewry CA, Morgan JE, Flanigan KM, Muntoni F. Dystrophin quantification: Biological and translational research implications. Neurology. 2014; 83(22):2062-9. PMID: 25355828

970. *Anthony K, Arechavala-Gomeza V, Ricotti V, Torelli S, Feng L, Janghra N, Tasca G, Guglieri M, Barresi R, Armaroli A, Ferlini A, Bushby K, Straub V, Ricci E, Sewry C, Morgan J, Muntoni F. Biochemical characterization of patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 skipping. JAMA Neurol. 2014; 71(1):32-40. PMID: 24217213

971. Srinivasan R, Rawlings D, Wood CL, Cheetham T, Moreno AC, Mayhew A, Eagle M, Guglieri M, Straub V, Owen C, Bushby K, Sarkozy A. Prophylactic oral bisphosphonate therapy in duchenne muscular dystrophy. Muscle Nerve. 2016;54:79-85. *Wood CL, Straub V, Guglieri M, Bushby K, Cheetham T. Short stature and pubertal delay in Duchenne muscular dystrophy. Arch Dis Child. 2015. PMID: 26141541

972. Palmio J, Evila A, Bashir A, Norwood F, Viitaniemi K, Vihola A, Huovinen S, Straub V, Hackman P, Hirano M, Bushby K, Udd B. Re-evaluation of the phenotype caused by the common MATR3 p.Ser85Cys mutation in a new family. J Neurol Neurosurg Psychiatry. 2015. PMID: 25952333

973. *Lynn S, Aartsma-Rus A, Bushby K, Furlong P, Goemans N, De Luca A, Mayhew A, McDonald C, Mercuri E, Muntoni F, Pohlschmidt M, Verschuuren J, Voit T, Vroom E, Wells DJ, Straub V. Measuring clinical effectiveness of medicinal products for the treatment of Duchenne muscular dystrophy. Neuromuscul Disord. 2015; 25(1):96-105. PMID: 25307856

974. Loughran T, Higgins DM, McCallum M, Coombs A, Straub V, Hollingsworth KG. Improving highly accelerated fat fraction measurements for clinical trials in muscular dystrophy: origin and quantitative effect of r2* changes. Radiology. 2015; 275(2):570-8. PMID: 25575118

95 | P a g e 975. Landfeldt E, Lindgren P, Bell C, Schmitt C, Guglieri M, Straub V, Lochmüller H, Bushby K. Compliance to Care Guidelines for Duchenne Muscular Dystrophy. J Neuromusc Dis. 2015; 2(1):63-72.

976. Heslop E, Csimma C, Straub V, McCall J, Nagaraju K, Wagner KR, Caizergues D, Korinthenberg R, Flanigan KM, Kaufmann P, McNeil E, Mendell J, Hesterlee S, Wells DJ, Bushby K, Tact. The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development. Orphanet J Rare Dis. 2015; 1049. PMID: 25902795

977. *Figueroa-Bonaparte S, Hudson J, Barresi R, Polvikoski T, Williams T, Topf A, Harris E, Hilton-Jones D, Petty R, Willis TA, Longman C, Dougan CF, Parton MJ, Hanna MG, Quinlivan R, Farrugia ME, Guglieri M, Bushby K, Straub V, Lochmüller H, Evangelista T. Mutational spectrum and phenotypic variability of VCP-related neurological disease in the UK. J Neurol Neurosurg Psychiatry. 2015. PMID: 26105173

978. Evangelista T, Bansagi B, Pyle A, Griffin H, Douroudis K, Polvikoski T, Antoniadi T, Bushby K, Straub V, Chinnery PF, Lochmüller H, Horvath R. Phenotypic variability of TRPV4 related neuropathies. Neuromuscul Disord. 2015; 25(6):516-21. PMID: 25900305

979. Blain AM, Greally E, Laval SH, Blamire AM, MacGowan GA, Straub VW. Assessment of ventricular function in mouse models of muscular dystrophy: a comparison of MRI with conductance catheter. Neuromuscul Disord. 2015; 25(1):24-31. PMID: 25454734

980. Blain A, Greally E, Laval SH, Blamire AM, MacGowan GA, Straub VW. Absence of Cardiac Benefit with Early Combination ACE Inhibitor and Beta Blocker Treatment in mdx Mice. J Cardiovasc Transl Res. 2015; 8(3):198-207. PMID: 25896492

981. Bladen CL, Salgado D, Monges S, Foncuberta ME, Kekou K, Kosma K, Dawkins H, Lamont L, Roy AJ, Chamova T, Guergueltcheva V, Chan S, Korngut L, Campbell C, Dai Y, Wang J, Barisic N, Brabec P, Lahdetie J, Walter MC, Schreiber-Katz O, Karcagi V, Garami M, Viswanathan V, Bayat F, Buccella F, Kimura E, Koeks Z, van den Bergen JC, Rodrigues M, Roxburgh R, Lusakowska A, Kostera-Pruszczyk A, Zimowski J, Santos R, Neagu E, Artemieva S, Rasic VM, Vojinovic D, Posada M, Bloetzer C, Jeannet PY, Joncourt F, Diaz- Manera J, Gallardo E, Karaduman AA, Topaloglu H, Sherif RE, Stringer A, Shatillo AV, Martin AS, Peay HL, Bellgard MI, Kirschner J, Flanigan KM, Straub V, Bushby K, Verschuuren J, Aartsma-Rus A, Beroud C, Lochmüller H. The TREAT-NMD DMD Global database: Analysis of More Than 7000 Duchenne Muscular Dystrophy Mutations. Hum Mutat. 2015; 36(4):395-402. PMID: 25604253

982. Barresi R, Morris C, Hudson J, Curtis E, Pickthall C, Bushby K, Davies NP, Straub V. Conserved expression of truncated telethonin in a patient with limb-girdle muscular dystrophy 2G. Neuromuscul Disord. 2015; 25(4):349-52. PMID: 25724973

983. Wood CL, Straub V, Guglieri M, Bushby K, Cheetham T. Short stature and pubertal delay in Duchenne muscular dystrophy. Arch Dis Child. 2016;101:101-106. PMID: 26141541 Vissing J, Barresi R, Witting N, Van Ghelue M, Gammelgaard L, Bindoff LA, Straub V, Lochmüller H, Hudson J, Wahl CM, Arnardottir S, Dahlbom K, Jonsrud C, Duno M. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy. Brain. 2016. PMID: 27259757

984. Straub V, Bertoli M. Where do we stand in trial readiness for autosomal recessive limb girdle muscular dystrophies? Neuromuscul Disord. 2016;26:111-125. PMID: 26810373

96 | P a g e 985. Thompson R, Straub V. Limb-girdle muscular dystrophies - international collaborations for translational research. Nat Rev Neurol. 2016;12:294-309. PMID: 27033376

986. *Straub V, Balabanov P, Bushby K, Ensini M, Goemans N, De Luca A, Pereda A, Hemmings R, Campion G, Kaye E, Arechavala-Gomeza V, Goyenvalle A, Niks E, Veldhuizen O, Furlong P, Stoyanova-Beninska V, Wood MJ, Johnson A, Mercuri E, Muntoni F, Sepodes B, Haas M, Vroom E, Aartsma-Rus A. Stakeholder cooperation to overcome challenges in orphan medicine development: the example of Duchenne muscular dystrophy. Lancet Neurol. 2016;15:882-890. PMID: 27302365

987. Scotton C, Bovolenta M, Schwartz E, Falzarano MS, Martoni E, Passarelli C, Armaroli A, Osman H, Rodolico C, Messina S, Pegoraro E, D'Amico A, Bertini E, Gualandi F, Neri M, Selvatici R, Boffi P, Maioli MA, Lochmüller H, Straub V, Bushby K, Castrignano T, Pesole G, Sabatelli P, Merlini L, Braghetta P, Bonaldo P, Bernardi P, Foley R, Cirak S, Zaharieva I, Muntoni F, Capitanio D, Gelfi C, Kotelnikova E, Yuryev A, Lebowitz M, Zhang X, Hodge BA, Esser KA, Ferlini A. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy. J Cell Sci. 2016;129:1671-1684. PMID: 26945058

988. Palmio J, Evila A, Bashir A, Norwood F, Viitaniemi K, Vihola A, Huovinen S, Straub V, Hackman P, Hirano M, Bushby K, Udd B. Re-evaluation of the phenotype caused by the common MATR3 p.Ser85Cys mutation in a new family. J Neurol Neurosurg Psychiatry. 2016;87:448-450. PMID: 25952333

989. Landfeldt E, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, Bushby K. Health-related quality of life in patients with Duchenne muscular dystrophy: a multinational, cross-sectional study. Dev Med Child Neurol. 2016;58:508-515. PMID: 26483095

990. Landfeldt E, Lindgren P, Bell CF, Guglieri M, Straub V, Lochmüller H, Bushby K. Quantifying the burden of caregiving in Duchenne muscular dystrophy. J Neurol. 2016;263:906-915. PMID: 26964543

991. Gainotti S, Turner C, Woods S, Kole A, McCormack P, Lochmüller H, Riess O, Straub V, Posada M, Taruscio D, Mascalzoni D. Improving the informed consent process in international collaborative rare disease research: effective consent for effective research. Eur J Hum Genet. 2016. PMID: 26860059

992. *Figueroa-Bonaparte S, Hudson J, Barresi R, Polvikoski T, Williams T, Topf A, Harris E, Hilton-Jones D, Petty R, Willis TA, Longman C, Dougan CF, Parton MJ, Hanna MG, Quinlivan R, Farrugia ME, Guglieri M, Bushby K, Straub V, Lochmüller H, Evangelista T. Mutational spectrum and phenotypic variability of VCP-related neurological disease in the UK. J Neurol Neurosurg Psychiatry. 2016;87:680-681. PMID: 26105173

Robert Taylor

993. Alston CL, Schaefer AM, Raman P, Solaroli N, Krishnan KJ, Blakely EL, He L, Craig K, Roberts M, Vyas A, Nixon J, Horvath R, Turnbull DM, Karlsson A, Gorman GS, Taylor RW. Late-onset respiratory failure due to TK2 mutations causing multiple mtDNA deletions. Neurology. 2013 Dec 3;81(23):2051-3. Epub 2013 Nov 6. PMID: 24198295

994. Spendiff S, Reza M, Murphy JL, Gorman G, Blakely EL, Taylor RW, Horvath R, Campbell G, Newman J, Lochmüller H, Turnbull DM. Mitochondrial DNA deletions in muscle satellite cells: implications for therapies. Hum Mol Genet. 2013 Dec 1;22(23):4739- 47. Epub 2013 Jul 11. PMID: 23847047

97 | P a g e 995. Jalil A, Usmani HA, Khan MI, Blakely EL, Taylor RW, Vassallo G, Ashworth J. Bilateral paediatric optic neuropathy precipitated by vitamin B12 deficiency and a novel mitochondrial DNA mutation. Int Ophthalmol. 2013 Dec;33(6):687-90. Epub 2013 Apr 10. PMID: 23572439

996. Spyropoulos A, Manford M, Horvath R, Alston CL, Yu-Wai-Man P, He L, Taylor RW, Chinnery PF. Near-identical segregation of mtDNA heteroplasmy in blood, muscle, urinary epithelium, and hair follicles in twins with optic atrophy, ptosis, and intractable epilepsy. JAMA Neurol. 2013 Dec;70(12):1552-5. PMID: 24126373

997. Baruffini E, Dallabona C, Invernizzi F, Yarham JW, Melchionda L, Blakely EL, Lamantea E, Donnini C, Santra S, Vijayaraghavan S, Roper HP, Burlina A, Kopajtich R, Walther A, Strom TM, Haack TB, Prokisch H, Taylor RW, Ferrero I, Zeviani M, Ghezzi D. MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast. Hum Mutat. 2013 Nov;34(11):1501- 9. Epub 2013 Sep 17. PMID: 23929671

998. Schaefer AM, Walker M, Turnbull DM, Taylor RW. Endocrine disorders in mitochondrial disease. Mol Cell Endocrinol. 2013 Oct 15;379(1-2):2-11. Epub 2013 Jun 13. Review. PMID: 23769710

999. Bates MG, Newman JH, Jakovljevic DG, Hollingsworth KG, Alston CL, Zalewski P, Klawe JJ, Blamire AM, MacGowan GA, Keavney BD, Bourke JP, Schaefer A, McFarland R, Newton JL, Turnbull DM, Taylor RW, Trenell MI, Gorman GS. Defining cardiac adaptations and safety of endurance training in patients with m.3243A>G-related mitochondrial disease. Int J Cardiol. 2013 Oct 9;168(4):3599-608. Epub 2013 Jun 3. PMID: 23742928

1000. Bonnen PE, Yarham JW, Besse A, Wu P, Faqeih EA, Al-Asmari AM, Saleh MA, Eyaid W, Hadeel A, He L, Smith F, Yau S, Simcox EM, Miwa S, Donti T, Abu-Amero KK, Wong LJ, Craigen WJ, Graham BH, Scott KL, McFarland R, Taylor RW. Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance. Am J Hum Genet. 2013 Sep 5;93(3):471-81. Epub 2013 Aug 29. Erratum in: Am J Hum Genet. 2013 Oct 3;93(4):773. PMID: 23993193

1001. Blakely EL, Yarham JW, Alston CL, Craig K, Poulton J, Brierley C, Park SM, Dean A, Xuereb JH, Anderson KN, Compston A, Allen C, Sharif S, Enevoldson P, Wilson M, Hammans SR, Turnbull DM, McFarland R, Taylor RW. Pathogenic mitochondrial tRNA point mutations: nine novel mutations affirm their importance as a cause of mitochondrial disease. Hum Mutat. 2013 Sep;34(9):1260-8. PMID: 23696415

10002. Al-Owain M, Colak D, Albakheet A, Al-Younes B, Al-Humaidi Z, Al-Sayed M, Al-Hindi H, Al-Sugair A, Al-Muhaideb A, Rahbeeni Z, Al-Sehli A, Al-Fadhli F, Ozand PT, Taylor RW, Kaya N. Clinical and biochemical features associated with BCS1L mutation. J Inherit Metab Dis. 2013 Sep;36(5):813-20. Epub 2012 Sep 19. PMID: 22991165

1003. Haack TB, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls TJ, Baruffini E, Walther A, Danhauser K, Zimmermann FA, Husain RA, Schum J, Mundy H, Ferrero I, Strom TM, Meitinger T, Taylor RW, Minczuk M, Mayr JA, Prokisch H. ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy. Am J Hum Genet. 2013 Aug 8;93(2):211-23. Epub 2013 Jul 11. PMID: 23849775

1004. *Nesbitt V, Pitceathly RD, Turnbull DM, Taylor RW, Sweeney MG, Mudanohwo EE, Rahman S, Hanna MG, McFarland R. The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation--implications

98 | P a g e for diagnosis and management. J Neurol Neurosurg Psychiatry. 2013 Aug;84(8):936-8. Epub 2013 Jan 25. PMID: 23355809

1005. Wedatilake Y, Brown RM, McFarland R, Yaplito-Lee J, Morris AA, Champion M, Jardine PE, Clarke A, Thorburn DR, Taylor RW, Land JM, Forrest K, Dobbie A, Simmons L, Aasheim ET, Ketteridge D, Hanrahan D, Chakrapani A, Brown GK, Rahman S. SURF1 deficiency: a multi-centre natural history study. Orphanet J Rare Dis. 2013 Jul 5;8:96. PMID: 23829769

1006. Bates MG, Hollingsworth KG, Newman JH, Jakovljevic DG, Blamire AM, MacGowan GA, Keavney BD, Chinnery PF, Turnbull DM, Taylor RW, Trenell MI, Gorman GS. Concentric hypertrophic remodelling and subendocardial dysfunction in mitochondrial DNA point mutation carriers. Eur Heart J Cardiovasc Imaging. 2013 Jul;14(7):650-8. Epub 2012 Nov 4. PMID: 23129433

1007. Giordano C, Perli E, Orlandi M, Pisano A, Tuppen HA, He L, Ierinò R, Petruzziello L, Terzi A, Autore C, Petrozza V, Gallo P, Taylor RW, d'Amati G. Cardiomyopathies due to homoplasmic mitochondrial tRNA mutations: morphologic and molecular features. Hum Pathol. 2013 Jul;44(7):1262-70. Epub 2013 Jan 17. PMID: 23332932

1008. Henderson M, De Waele L, Hudson J, Eagle M, Sewry C, Marsh J, Charlton R, He L, Blakely EL, Horrocks I, Stewart W, Taylor RW, Longman C, Bushby K, Barresi R. Recessive desmin-null muscular dystrophy with central nuclei and mitochondrial abnormalities. Acta Neuropathol. 2013 Jun;125(6):917-9. Epub 2013 Apr 11. PMID: 23575897

1009. Campbell GR, Reeve A, Ziabreva I, Polvikoski TM, Taylor RW, Reynolds R, Turnbull DM, Mahad DJ. Mitochondrial DNA deletions and depletion within paraspinal muscles. Neuropathol Appl Neurobiol. 2013 Jun;39(4):377-89. PMID: 22762368

1010. Elson JL, Cadogan M, Apabhai S, Whittaker RG, Phillips A, Trennell MI, Horvath R, Taylor RW, McFarland R, McColl E, Turnbull DM, Gorman GS. Initial development and validation of a mitochondrial disease quality of life scale. Neuromuscul Disord. 2013 Apr;23(4):324-9. Epub 2013 Feb 20. PMID: 23433484

1011. Whittaker RG, Hall E, Mansoor MK, Taylor RW, Turnbull DM. Incidence of carpal tunnel syndrome in adult patients with mitochondrial disease. J Peripher Nerv Syst. 2013 Mar;18(1):59-61. PMID: 23521646

1012. Yarham JW, Blakely EL, Alston CL, Roberts ME, Ealing J, Pal P, Turnbull DM, McFarland R, Taylor RW. The m.3291T>C mt-tRNA(Leu(UUR)) mutation is definitely pathogenic and causes multisystem mitochondrial disease. J Neurol Sci. 2013 Feb 15;325(1-2):165-9. Epub 2012 Dec 27. PMID:23273904

1013. Lax NZ, Gnanapavan S, Dowson SJ, Alston CL, He L, Polvikoski TM, Jaros E, O'Donovan DG, Yarham JW, Turnbull DM, Dean AF, Taylor RW. Early-onset cataracts, spastic paraparesis, and ataxia caused by a novel mitochondrial tRNAGlu (MT-TE) gene mutation causing severe complex I deficiency: a clinical, molecular, and neuropathologic study. J Neuropathol Exp Neurol. 2013 Feb;72(2):164-75. PMID: 23334599

1014. Payne BA, Wilson IJ, Yu-Wai-Man P, Coxhead J, Deehan D, Horvath R, Taylor RW, Samuels DC, Santibanez-Koref M, Chinnery PF. Universal heteroplasmy of human mitochondrial DNA. Hum Mol Genet. 2013 Jan 15;22(2):384-90. Epub 2012 Oct 16. PMID: 23077218

99 | P a g e 1015. Kinghorn KJ, Kaliakatsos M, Blakely EL, Taylor RW, Rich P, Clarke A, Omer S. Hypertrophic olivary degeneration on magnetic resonance imaging in mitochondrial syndromes associated with POLG and SURF1 mutations. J Neurol. 2013 Jan;260(1):3-9. Epub 2012 Jun 24. Review. PMID: 22729384

1016. Yu-Wai-Man C, Smith FE, Firbank MJ, Guthrie G, Guthrie S, Gorman GS, Taylor RW, Turnbull DM, Griffiths PG, Blamire AM, Chinnery PF, Yu-Wai-Man P. Extraocular muscle atrophy and central nervous system involvement in chronic progressive external ophthalmoplegia. PLoS One. 2013 Sep 27;8(9):e75048. eCollection 2013. PMID: 24086434

1017. Smith PM, Elson JL, Greaves LC, Wortmann SB, Rodenburg RJ, Lightowlers RN, Chrzanowska-Lightowlers ZM, Taylor RW, Vila-Sanjurjo A. The role of the mitochondrial in human disease: searching for mutations in 12S mitochondrial rRNA with high disruptive potential. Hum Mol Genet. 2014 Feb 15;23(4):949-67. Epub 2013 Oct 2. PMID: 24092330

1018. Almalki A, Alston CL, Parker A, Simonic I, Mehta SG, He L, Reza M, Oliveira JM, Lightowlers RN, McFarland R, Taylor RW, Chrzanowska-Lightowlers ZM. Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency. Biochim Biophys Acta. 2014 Jan;1842(1):56-64. Epub 2013 Oct 24. PMID: 24161539

1019. Grady JP, Campbell G, Ratnaike T, Blakely EL, Falkous G, Nesbitt V, Schaefer AM, McNally RJ, Gorman GS, Taylor RW, Turnbull DM, McFarland R. Disease progression in patients with single, large-scale mitochondrial DNA deletions. Brain. 2014 Feb;137(Pt 2):323-34. Epub 2013 Nov 25. PMID: 24277717

1020. Perli E, Giordano C, Pisano A, Montanari A, Campese AF, Reyes A, Ghezzi D, Nasca A, Tuppen HA, Orlandi M, Di Micco P, Poser E, Taylor RW, Colotti G, Francisci S, Morea V, Frontali L, Zeviani M, d'Amati G. The isolated carboxy-terminal domain of human mitochondrial leucyl-tRNA synthetase rescues the pathological phenotype of mitochondrial tRNA mutations in human cells. EMBO Mol Med. 2014 Feb;6(2):169-82. Epub 2014 Jan 10. PMID: 24413190

1021. Uusimaa J, Evans J, Smith C, Butterworth A, Craig K, Ashley N, Liao C, Carver J, Diot A, Macleod L, Hargreaves I, Al-Hussaini A, Faqeih E, Asery A, Al Balwi M, Eyaid W, Al-Sunaid A, Kelly D, van Mourik I, Ball S, Jarvis J, Mulay A, Hadzic N, Samyn M, Baker A, Rahman S, Stewart H, Morris AA, Seller A, Fratter C, Taylor RW, Poulton J. Clinical, biochemical, cellular and molecular characterization of mitochondrial DNA depletion syndrome due to novel mutations in the MPV17 gene. Eur J Hum Genet. 2014 Feb;22(2):184-91. Epub 2013 May 29. PMID: 23714749

1022. Pyle A, Ramesh V, Bartsakoulia M, Boczonadi V, Gomez-Duran A, Herczegfalvi A, Blakely EL, Smertenko T, Duff J, Eglon G, Moore D, Yu-Wai-Man P, Douroudis K, Santibanez-Koref M, Griffin H, Lochmüller H, Karcagi V, Taylor RW, Chinnery PF, Horvath R. Behr's Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in the C12orf65 Gene. J Neuromuscul Dis. 2014;1(1):55-63. PMID: 26380172

1023. Grady JP, Murphy JL, Blakely EL, Haller RG, Taylor RW, Turnbull DM, Tuppen HA. Accurate measurement of mitochondrial DNA deletion level and copy number differences in human skeletal muscle. PLoS One. 2014 Dec 4;9(12):e114462. eCollection 2014. PMID: 25474153

1024. Lehmann D, Schubert K, Joshi PR, Baty K, Blakely EL, Zierz S, Taylor RW,

100 | P a g e Deschauer M. A novel m.7539C>T point mutation in the mt-tRNA(Asp) gene associated with multisystemic mitochondrial disease. Neuromuscul Disord. 2015 Jan;25(1):81-4. Epub 2014 Sep 28. PMID: 25447692

1025. *Di Foggia V, Zhang X, Licastro D, Gerli MF, Phadke R, Muntoni F, Mourikis P, Tajbakhsh S, Ellis M, Greaves LC, Taylor RW, Cossu G, Robson LG, Marino S. Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy. J Exp Med. 2014 Dec 15;211(13):2617-33. Epub 2014 Dec 1. PMID:25452464

1026. Kopajtich R, Nicholls TJ, Rorbach J, Metodiev MD, Freisinger P, Mandel H, Vanlander A, Ghezzi D, Carrozzo R, Taylor RW, Marquard K, Murayama K, Wieland T, Schwarzmayr T, Mayr JA, Pearce SF, Powell CA, Saada A, Ohtake A, Invernizzi F, Lamantea E, Sommerville EW, Pyle A, Chinnery PF, Crushell E, Okazaki Y, Kohda M, Kishita Y, Tokuzawa Y, Assouline Z, Rio M, Feillet F, Mousson de Camaret B, Chretien D, Munnich A, Menten B, Sante T, Smet J, Régal L, Lorber A, Khoury A, Zeviani M, Strom TM, Meitinger T, Bertini ES, Van Coster R, Klopstock T, Rötig A, Haack TB, Minczuk M, Prokisch H. Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy. Am J Hum Genet. 2014 Dec 4;95(6):708-20. Epub 2014 Nov 26. PMID: 25434004

1027. Griffin HR, Pyle A, Blakely EL, Alston CL, Duff J, Hudson G, Horvath R, Wilson IJ, Santibanez-Koref M, Taylor RW, Chinnery PF. Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations. Genet Med. 2014 Dec;16(12):962-71. Epub 2014 Jun 5. PMID: 24901348

1028. Nesbitt V, Alston CL, Blakely EL, Fratter C, Feeney CL, Poulton J, Brown GK, Turnbull DM, Taylor RW, McFarland R. A national perspective on prenatal testing for mitochondrial disease. Eur J Hum Genet. 2014 Nov;22(11):1255-9. Epub 2014 Mar 19. PMID: 24642831

1029. Balreira A, Boczonadi V, Barca E, Pyle A, Bansagi B, Appleton M, Graham C, Hargreaves IP, Rasic VM, Lochmüller H, Griffin H, Taylor RW, Naini A, Chinnery PF, Hirano M, Quinzii CM, Horvath R. ANO10 mutations cause ataxia and coenzyme Q deficiency. J Neurol. 2014 Nov;261(11):2192-8 Epub 2014 Sep 3. PMID: 25182700

1030.₁₀ Melchionda L, Haack TB, Hardy S, Abbink TE, Fernandez-Vizarra E, Lamantea E, Marchet S, Morandi L, Moggio M, Carrozzo R, Torraco A, Diodato D, Strom TM, Meitinger T, Tekturk P, Yapici Z, Al-Murshedi F, Stevens R, Rodenburg RJ, Lamperti C, Ardissone A, Moroni I, Uziel G, Prokisch H, Taylor RW, Bertini E, van der Knaap MS, Ghezzi D, Zeviani M. Mutations in APOPT1, encoding a mitochondrial protein, cause cavitating leukoencephalopathy with cytochrome c oxidase deficiency. Am J Hum Genet. 2014 Sep 4;95(3):315-25. Epub 2014 Aug 28. PMID: 25175347

1031. Campbell G, Krishnan KJ, Deschauer M, Taylor RW, Turnbull DM. Dissecting the mechanisms underlying the accumulation of mitochondrial DNA deletions in human skeletal muscle. Hum Mol Genet. 2014 Sep 1;23(17):4612-20. Epub 2014 Apr 15. PMID: 24740879

1032. Greaves LC, Nooteboom M, Elson JL, Tuppen HA, Taylor GA, Commane DM, Arasaradnam RP, Khrapko K, Taylor RW, Kirkwood TB, Mathers JC, Turnbull DM. Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing. PLoS Genet. 2014 Sep 18;10(9):e1004620. eCollection 2014 Sep. PMID: 25232829

101 | P a g e 1033. Haghighi A, Haack TB, Atiq M, Mottaghi H, Haghighi-Kakhki H, Bashir RA, Ahting U, Feichtinger RG, Mayr JA, Rötig A, Lebre AS, Klopstock T, Dworschak A, Pulido N, Saeed MA, Saleh-Gohari N, Holzerova E, Chinnery PF, Taylor RW, Prokisch H. Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients. Orphanet J Rare Dis. 2014 Aug 20;9:119. Review. PMID: 25208612

1034. Grünewald A, Lax NZ, Rocha MC, Reeve AK, Hepplewhite PD, Rygiel KA, Taylor RW, Turnbull DM. Quantitative quadruple-label immunofluorescence of mitochondrial and cytoplasmic proteins in single neurons from human midbrain tissue. J Neurosci Methods. 2014 Jul 30;232:143-9. Epub 2014 May 29. PMID: 24880043

1035. Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski-Feder E, Abicht A, Czermin B, Kleinle S, Morris AA, Vassallo G, Gorman GS, Ramesh V, Turnbull DM, Santibanez-Koref M, McFarland R, Horvath R, Chinnery PF. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA. 2014 Jul 2;312(1):68-77. PMID: 25058219

1036. Blakely EL, Alston CL, Lecky B, Chakrabarti B, Falkous G, Turnbull DM, Taylor RW, Gorman GS. Distal weakness with respiratory insufficiency caused by the m.8344A > G "MERRF" mutation. Neuromuscul Disord. 2014 Jun;24(6):533-6. Epub 2014 Apr 1. PMID: 24792523

1037. Yarham JW, Lamichhane TN, Pyle A, Mattijssen S, Baruffini E, Bruni F, Donnini C, Vassilev A, He L, Blakely EL, Griffin H, Santibanez-Koref M, Bindoff LA, Ferrero I, Chinnery PF, McFarland R, Maraia RJ, Taylor RW. Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA. PLoS Genet. 2014 Jun 5;10(6):e1004424. eCollection 2014 Jun. PMID: 24901367

1038. Pfeffer G, Gorman GS, Griffin H, Kurzawa-Akanbi M, Blakely EL, Wilson I, Sitarz K, Moore D, Murphy JL, Alston CL, Pyle A, Coxhead J, Payne B, Gorrie GH, Longman C, Hadjivassiliou M, McConville J, Dick D, Imam I, Hilton D, Norwood F, Baker MR, Jaiser SR, Yu-Wai-Man P, Farrell M, McCarthy A, Lynch T, McFarland R, Schaefer AM, Turnbull DM, Horvath R, Taylor RW, Chinnery PF. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. Brain. 2014 May;137(Pt 5):1323-36. Epub 2014 Apr 10. PMID: 24727571

1039. Keogh MJ, Daud D, Pyle A, Duff J, Griffin H, He L, Alston CL, Steele H, Taggart S, Basu AP, Taylor RW, Horvath R, Ramesh V, Chinnery PF. A novel de novo STXBP1 mutation is associated with mitochondrial complex I deficiency and late-onset juvenile-onset parkinsonism. Neurogenetics. 2015 Jan;16(1):65-7. Epub 2014 Nov 25. PMID: 25418441

1040. Whittaker RG, Devine HE, Gorman GS, Schaefer AM, Horvath R, Ng Y, Nesbitt V, Lax NZ, McFarland R, Cunningham MO, Taylor RW, Turnbull DM. Epilepsy in adults with mitochondrial disease: A cohort study. Ann Neurol. 2015 Dec;78(6):949-57. Epub 2015 Nov 17. PMID: 26381753

1041. Oláhová M, Hardy SA, Hall J, Yarham JW, Haack TB, Wilson WC, Alston CL, He L, Aznauryan E, Brown RM, Brown GK, Morris AA, Mundy H, Broomfield A, Barbosa IA,

102 | P a g e Simpson MA, Deshpande C, Moeslinger D, Koch J, Stettner GM, Bonnen PE, Prokisch H, Lightowlers RN, McFarland R, Chrzanowska-Lightowlers ZM, Taylor RW. LRPPRC mutations cause early-onset multisystem mitochondrial disease outside of the French-Canadian population. Brain. 2015 Dec;138(Pt 12):3503-19. Epub 2015 Oct 27. PMID: 26510951

1042. Lehmann D, Schubert K, Joshi PR, Hardy SA, Tuppen HA, Baty K, Blakely EL, Bamberg C, Zierz S, Deschauer M, Taylor RW. Pathogenic mitochondrial mt-tRNA(Ala) variants are uniquely associated with isolated myopathy. Eur J Hum Genet. 2015 Dec;23(12):1735-8. Epub 2015 Apr 15. PMID: 25873012

1043. Elson JL, Smith PM, Greaves LC, Lightowlers RN, Chrzanowska-Lightowlers ZM, Taylor RW, Vila-Sanjurjo A. The presence of highly disruptive 16S rRNA mutations in clinical samples indicates a wider role for mutations of the mitochondrial ribosome in human disease. Mitochondrion. 2015 Nov;25:17-27. Epub 2015 Sep 5. PMID: 26349026

1044. Rocha MC, Grady JP, Grünewald A, Vincent A, Dobson PF, Taylor RW, Turnbull DM, Rygiel KA. A novel immunofluorescent assay to investigate oxidative phosphorylation deficiency in mitochondrial myopathy: understanding mechanisms and improving diagnosis. Sci Rep. 2015 Oct 15;5:15037.PMID: 26469001

1045. Lightowlers RN, Taylor RW, Turnbull DM. Mutations causing mitochondrial disease: What is new and what challenges remain? Science. 2015 Sep 25;349(6255):1494-9. Epub 2015 Sep 24. Review. PMID: 26404827.

1046. Huemer M, Karall D, Schossig A, Abdenur JE, Al Jasmi F, Biagosch C, Distelmaier F, Freisinger P, Graham BH, Haack TB, Hauser N, Hertecant J, Ebrahimi-Fakhari D, Konstantopoulou V, Leydiker K, Lourenco CM, Scholl-Bürgi S, Wilichowski E, Wolf NI, Wortmann SB, Taylor RW, Mayr JA, Bonnen PE, Sperl W, Prokisch H, McFarland R. Clinical, morphological, biochemical, imaging and outcome parameters in 21 individuals with mitochondrial maintenance defect related to FBXL4 mutations. J Inherit Metab Dis. 2015 Sep;38(5):905-14 Epub 2015 Apr 14. PMID: 25868664

1047. Powell CA, Kopajtich R, D'Souza AR, Rorbach J, Kremer LS, Husain RA, Dallabona C, Donnini C, Alston CL, Griffin H, Pyle A, Chinnery PF, Strom TM, Meitinger T, Rodenburg RJ, Schottmann G, Schuelke M, Romain N, Haller RG, Ferrero I, Haack TB, Taylor RW, Prokisch H, Minczuk M. TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies. Am J Hum Genet. 2015 Aug 6;97(2):319-28. Epub 2015 Jul 16. PMID: 26189817

1048. Alston CL, Ceccatelli Berti C, Blakely EL, Oláhová M, He L, McMahon CJ, Olpin SE, Hargreaves IP, Nolli C, McFarland R, Goffrini P, O'Sullivan MJ, Taylor RW.A recessive homozygous p.Asp92Gly SDHD mutation causes prenatal cardiomyopathy and a severe mitochondrial complex II deficiency. Hum Genet. 2015 Aug;134(8):869-79. Epub 2015 May 26. PMID: 26008905

1049. Lax NZ, Alston CL, Schon K, Park SM, Krishnakumar D, He L, Falkous G, Ogilvy-Stuart A, Lees C, King RH, Hargreaves IP, Brown GK, McFarland R, Dean AF, Taylor RW. Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations. J Neuropathol Exp Neurol. 2015 Jul;74(7):688-703. PMID:26083569

103 | P a g e 1050. Gorman GS, Blakely EL, Hornig-Do HT, Tuppen HA, Greaves LC, He L, Baker A, Falkous G, Newman J, Trenell MI, Lecky B, Petty RK, Turnbull DM, McFarland R, Taylor RW. Novel MTND1 mutations cause isolated exercise intolerance, complex I deficiency and increased assembly factor expression. Clin Sci (Lond). 2015 Jun;128(12):895-904. PMID: 25626417

1051. Olpin SE, Murphy E, Kirk RJ, Taylor RW, Quinlivan R. The investigation and management of metabolic myopathies. J Clin Pathol. 2015 Jun;68(6):410-7. Epub 2015 Apr 15. PMID: 25878327

1052. Hanisch F, Kornhuber M, Alston CL, Taylor RW, Deschauer M, Zierz S. SANDO syndrome in a cohort of 107 patients with CPEO and mitochondrial DNA deletions. J Neurol Neurosurg Psychiatry. 2015 Jun;86(6):630-4.Epub 2014 Aug 20. PMID: 25143630

1053. Rygiel KA, Grady JP, Taylor RW, Tuppen HA, Turnbull DM. Triplex real-time PCR--an improved method to detect a wide spectrum of mitochondrial DNA deletions in single cells. Sci Rep. 2015 May 19;5:9906. PMID: 25989140

1054. Haack TB, Jackson CB, Murayama K, Kremer LS, Schaller A, Kotzaeridou U, de Vries MC, Schottmann G, Santra S, Büchner B, Wieland T, Graf E, Freisinger P, Eggimann S, Ohtake A, Okazaki Y, Kohda M, Kishita Y, Tokuzawa Y, Sauer S, Memari Y, Kolb-Kokocinski A, Durbin R, Hasselmann O, Cremer K, Albrecht B, Wieczorek D, Engels H, Hahn D, Zink AM, Alston CL, Taylor RW, Rodenburg RJ, Trollmann R, Sperl W, Strom TM, Hoffmann GF, Mayr JA, Meitinger T, Bolognini R, Schuelke M, Nuoffer JM, Kölker S, Prokisch H, Klopstock T. Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement. Ann Clin Transl Neurol. 2015 May;2(5):492-509. Epub 2015 Mar 13. PMID: 26000322

1055. Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, Taylor RW, Turnbull DM, McFarland R. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015 May;77(5):753-9.. Epub 2015 Mar 28. PMID: 25652200

1056. Payne BA, Gardner K, Blakely EL, Maddison P, Horvath R, Taylor RW,Chinnery PF. Clinical and pathological features of mitochondrial DNA deletion disease following antiretroviral treatment. JAMA Neurol. 2015 May;72(5):603-5. PMID: 25961175

1057. Rygiel KA, Miller J, Grady JP, Rocha MC, Taylor RW, Turnbull DM. Mitochondrial and inflammatory changes in sporadic inclusion body myositis. Neuropathol Appl Neurobiol. 2015 Apr;41(3):288-303. PMID: 24750247

1058. Besse A, Wu P, Bruni F, Donti T, Graham BH, Craigen WJ, McFarland R, Moretti P, Lalani S, Scott KL, Taylor RW, Bonnen PE. The GABA transaminase, ABAT, is essential for mitochondrial nucleoside metabolism. Cell Metab. 2015 Mar 3;21(3):417-27. PMID: 25738457

1059. *Hall AM, Vilasi A, Garcia-Perez I, Lapsley M, Alston CL, Pitceathly RD, McFarland R, Schaefer AM, Turnbull DM, Beaumont NJ, Hsuan JJ, Cutillas PR, Lindon JC, Holmes E, Unwin RJ, Taylor RW, Gorman GS, Rahman S, Hanna MG. The urinary proteome and metabonome differ from normal in adults with mitochondrial disease. Kidney Int. 2015 Mar;87(3):610-22. Epub 2014 Sep 10 PMID: 25207879

104 | P a g e 1060. McCann BJ, Tuppen HA, Küsters B, Lammens M, Smeitink JA, Taylor RW, Rodenburg RJ, Wortmann SB. A novel mitochondrial DNA m.7507A>G mutation is only pathogenic at high levels of heteroplasmy. Neuromuscul Disord. 2015 Mar;25(3):262-7. Epub 2014 Nov 13. PMID: 25497401

1061. Gorman GS, Grady JP, Ng Y, Schaefer AM, McNally RJ, Chinnery PF, Yu-Wai-Man P, Herbert M, Taylor RW, McFarland R, Turnbull DM. Mitochondrial donation--how many women could benefit? N Engl J Med. 2015 Feb 26;372(9):885-7. Epub 2015 Jan 28. PMID: 25629662

1062. Bargiela D, Shanmugarajah P, Lo C, Blakely EL, Taylor RW, Horvath R, Wharton S, Chinnery PF, Hadjivassiliou M. Mitochondrial pathology in progressive cerebellar ataxia. Cerebellum Ataxias. 2015 Dec 4;2:16. eCollection 2015. PMID: 26640698 Brito S, Thompson K, Campistol J, Colomer J, Hardy SA, He L, Fernández-Marmiesse A, Palacios L, Jou C, Jiménez-Mallebrera C, Armstrong J, Montero R, Artuch R, Tischner C, Wenz T, McFarland R, Taylor RW. Corrigendum: Long-term survival in a child with severe encephalopathy, multiple respiratory chain deficiency and GFM1 mutations. Front Genet. 2015 Jul 28;6:254. eCollection 2015. PMID: 26284110

1063. Brito S, Thompson K, Campistol J, Colomer J, Hardy SA, He L, Fernández-Marmiesse A, Palacios L, Jou C, Jiménez-Mallebrera C, Armstrong J, Montero R, Artuch R, Tischner C, Wenz T, McFarland R, Taylor RW. Long-term survival in a child with severe encephalopathy, multiple respiratory chain deficiency and GFM1 mutations. Front Genet. 2015 Mar 23;6:102. eCollection 2015. Erratum in: Front Genet. 2015;6:254. PMID: 25852744

1064. Gorman GS, Pfeffer G, Griffin H, Blakely EL, Kurzawa-Akanbi M, Gabriel J, Sitarz K, Roberts M, Schoser B, Pyle A, Schaefer AM, McFarland R, Turnbull DM, Horvath R, Chinnery PF, Taylor RW. Clonal expansion of secondary mitochondrial DNA deletions associated with spinocerebellar ataxia type 28. JAMA Neurol. 2015 Jan;72(1):106-11. PMID: 25420100

1065. Perli E, Fiorillo A, Giordano C, Pisano A, Montanari A, Grazioli P, Campese AF, Di Micco P, Tuppen HA, Genovese I, Poser E, Preziuso C, Taylor RW, Morea V, Colotti G, d'Amati G. Short peptides from leucyl-tRNA synthetase rescue disease-causing mitochondrial tRNA point mutations. Hum Mol Genet. 2016 Mar 1;25(5):903-15. Epub 2015 Dec 31. PMID: 26721932

1066. Carrozzo R, Verrigni D, Rasmussen M, de Coo R, Amartino H, Bianchi M, Buhas D, Mesli S, Naess K, Born AP, Woldseth B, Prontera P, Batbayli M, Ravn K, Joensen F, Cordelli DM, Santorelli FM, Tulinius M, Darin N, Duno M, Jouvencel P, Burlina A, Stangoni G, Bertini E, Redonnet-Vernhet I, Wibrand F, Dionisi-Vici C, Uusimaa J, Vieira P, Osorio AN, McFarland R, Taylor RW, Holme E, Ostergaard E. Succinate-CoA ligase deficiency due to mutations in SUCLA2 and SUCLG1: phenotype and genotype correlations in 71 patients. J Inherit Metab Dis. 2016 Mar;39(2):243-52. Epub 2015 Oct 16. PMID: 26475597

1067. de Laat P, Janssen MC, Alston CL, Taylor RW, Rodenburg RJ, Smeitink JA. Three families with 'de novo' m.3243A > G mutation. BBA Clin. 2016 Apr 29;6:19-24 eCollection 2016 Dec. PMID: 27331024

1068. Kennedy H, Haack TB, Hartill V, Mataković L, Baumgartner ER, Potter H, Mackay R, Alston CL, O'Sullivan S, McFarland R, Connolly G, Gannon C, King R, Mead S,

105 | P a g e Crozier I, Chan W, Florkowski CM, Sage M, Höfken T, Alhaddad B, Kremer LS, Kopajtich R, Feichtinger RG, Sperl W, Rodenburg RJ, Minet JC, Dobbie A, Strom TM, Meitinger T, George PM, Johnson CA, Taylor RW, Prokisch H, Doudney K, Mayr JA. Sudden Cardiac Death Due to Deficiency of the Mitochondrial Inorganic Pyrophosphatase PPA2. Am J Hum Genet. 2016 Sep 1;99(3):674-82. Epub 2016 Aug 11. PMID: 27523597

1069. Alston CL, Howard C, Oláhová M, Hardy SA, He L, Murray PG, O'Sullivan S, Doherty G, Shield JP, Hargreaves IP, Monavari AA, Knerr I, McCarthy P, Morris AA, Thorburn DR, Prokisch H, Clayton PE, McFarland R, Hughes J, Crushell E, Taylor RW. A recurrent mitochondrial p.Trp22Arg NDUFB3 variant causes a distinctive facial appearance, short stature and a mild biochemical and clinical phenotype. J Med Genet. 2016 Sep;53(9):634-41. Epub 2016 Apr 18. PMID: 27091925

1070. Anagnostou ME, Ng YS, Taylor RW, McFarland R. Epilepsy due to mutations in the mitochondrial polymerase gamma (POLG) gene: A clinical and molecular genetic review. Epilepsia. 2016 Aug 24. [Epub ahead of print] Review. PMID: 27554452

1071. Ng YS, Grady JP, Lax NZ, Bourke JP, Alston CL, Hardy SA, Falkous G, Schaefer AG, Radunovic A, Mohiddin SA, Ralph M, Alhakim A, Taylor RW, McFarland R, Turnbull DM, Gorman GS. Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults. Eur Heart J. 2016 Aug 21;37(32):2552-9. Epub 2015 Jul 17. PMID: 26188002

1072. Floyd BJ, Wilkerson EM, Veling MT, Minogue CE, Xia C, Beebe ET, Wrobel RL, Cho H, Kremer LS, Alston CL, Gromek KA, Dolan BK, Ulbrich A, Stefely JA, Bohl SL, Werner KM, Jochem A, Westphall MS, Rensvold JW, Taylor RW, Prokisch H, Kim JJ, Coon JJ, Pagliarini DJ. Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function. Mol Cell. 2016 Aug 18;63(4):621-32. doi: 10.1016/j.molcel.2016.06.033. Epub 2016 Aug 4. PMID: 27499296

1073. Ng YS, Hardy SA, Shrier V, Quaghebeur G, Mole DR, Daniels MJ, Downes SM, Freebody J, Fratter C, Hofer M, Nemeth AH, Poulton J, Taylor RW. Clinical features of the pathogenic m.5540G>A mitochondrial transfer RNA tryptophan gene mutation. Neuromuscul Disord. 2016 Aug 17. [Epub ahead of print] PMID: 27618137

1074. Vincent AE, Grady JP, Rocha MC, Alston CL, Rygiel KA, Barresi R, Taylor RW, Turnbull DM. Mitochondrial dysfunction in myofibrillar myopathy. Neuromuscul Disord. 2016 Aug 10. pii: S0960-8966(16)30160-2. [Epub ahead of print] PMID: 27618136

1075. Vincent AE, Ng YS, White K, Davey T, Mannella C, Falkous G, Feeney C, Schaefer AM, McFarland R, Gorman GS, Taylor RW, Turnbull DM, Picard M. The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy. Sci Rep. 2016 Aug 10;6:30610. PMID: 27506553

1076. Ehinger JK, Piel S, Ford R, Karlsson M, Sjövall F, Frostner EÅ, Morota S, Taylor RW, Turnbull DM, Cornell C, Moss SJ, Metzsch C, Hansson MJ, Fliri H, Elmér E. Cell-permeable succinate prodrugs bypass mitochondrial complex I deficiency. Nat Commun. 2016 Aug 9;7:12317. PMID: 27502960

1077. Hardy SA, Blakely EL, Purvis AI, Rocha MC, Ahmed S, Falkous G, Poulton J, Rose MR, O'Mahony O, Bermingham N, Dougan CF, Ng YS, Horvath R, Turnbull DM, Gorman GS, Taylor RW. Pathogenic mtDNA mutations causing mitochondrial myopathy: The need for muscle biopsy. Neurol Genet. 2016 Jun 23;2(4):e82. eCollection 2016 Aug. PMID: 27536729

106 | P a g e 1078. Chrysostomou A, Grady JP, Laude A, Taylor RW, Turnbull DM, Lax NZ. Investigating complex I deficiency in Purkinje cells and in patients with mitochondrial disease. Neuropathol Appl Neurobiol. 2016 Aug;42(5):477-92. Epub 2015 Sep 30. PMID: 26337858

1079. McKiernan P, Ball S, Santra S, Foster K, Fratter C, Poulton J, Craig K, McFarland R, Rahman S, Hargreaves I, Gupte G, Sharif K, Taylor RW. Incidence of Primary Mitochondrial Disease in Children Presenting With Acute Liver Failure Under 2 Years of Age. J Pediatr Gastroenterol Nutr. 2016 Jul 30. [Epub ahead of print] PMID: 27482763

1080. Ng YS, Feeney C, Schaefer AM, Holmes CE, Hynd P, Alston CL, Grady JP, Roberts M, Maguire M, Bright A, Taylor RW, Yiannakou Y, McFarland R, Turnbull DM, Gorman GS. Pseudo-obstruction, stroke and mitochondrial dysfunction: A lethal combination. Ann Neurol. 2016 Jul 25. [Epub ahead of print] PMID: 27453452

1081. Sallevelt SC, de Die-Smulders CE, Hendrickx AT, Hellebrekers DM, de Coo IF, Alston CL, Knowles C, Taylor RW, McFarland R, Smeets HJ. De novo mtDNA point mutations are common and have a low recurrence risk. J Med Genet. 2016 Jul 22. [Epub ahead of print] PMID: 27450679

1082. Ng YS, Alston CL, Diodato D, Morris AA, Ulrick N, Kmoch S, Houštěk J, Martinelli D, Haghighi A, Atiq M, Gamero MA, Garcia-Martinez E, Kratochvílová H, Santra S, Brown RM, Brown GK, Ragge N, Monavari A, Pysden K, Ravn K, Casey JP, Khan A, Chakrapani A, Vassallo G, Simons C, McKeever K, O'Sullivan S, Childs AM, Østergaard E, Vanderver A, Goldstein A, Vogt J, Taylor RW, McFarland R. The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease. J Med Genet. 2016 Jul 13. [Epub ahead of print] PMID: 27412952

1083. Metodiev MD, Thompson K, Alston CL, Morris AA, He L, Assouline Z, Rio M, Bahi-Buisson N, Pyle A, Griffin H, Siira S, Filipovska A, Munnich A, Chinnery PF, McFarland R, Rötig A, Taylor RW. Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies. Am J Hum Genet. 2016 Jul 7;99(1):246. PMID:27392079

1084. Alston CL, Compton AG, Formosa LE, Strecker V, Oláhová M, Haack TB, Smet J, Stouffs K, Diakumis P, Ciara E, Cassiman D, Romain N, Yarham JW, He L, De Paepe B, Vanlander AV, Seneca S, Feichtinger RG, Płoski R, Rokicki D, Pronicka E, Haller RG, Van Hove JL, Bahlo M, Mayr JA, Van Coster R, Prokisch H, Wittig I, Ryan MT, Thorburn DR, Taylor RW. Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype. Am J Hum Genet. 2016 Jul 7;99(1):217-27. Epub 2016 Jun 30. PMID:27374774

1085. Mathieu L, Costa AL, Le Bachelier C, Slama A, Lebre AS, Taylor RW, Bastin J, Djouadi F. Resveratrol attenuates oxidative stress in mitochondrial Complex I deficiency: Involvement of SIRT3. Free Radic Biol Med. 2016 Jul;96:190-8. Epub 2016 Apr 25. PMID: 27126960

1086. Gupta A, Colmenero I, Ragge NK, Blakely EL, He L, McFarland R, Taylor RW, Vogt J, Milford DV. Compound heterozygous RMND1 gene variants associated with chronic kidney disease, dilated cardiomyopathy and neurological involvement: a case report. BMC Res Notes. 2016 Jun 27;9:325. PMID: 27350610

1087. Rygiel KA, Tuppen HA, Grady JP, Vincent A, Blakely EL, Reeve AK, Taylor RW,

107 | P a g e Picard M, Miller J, Turnbull DM. Complex mitochondrial DNA rearrangements in individual cells from patients with sporadic inclusion body myositis. Nucleic Acids Res. 2016 Jun 20;44(11):5313-29. Epub 2016 Apr 30. PMID: 27131788

1088. Kullar PJ, Quail J, Lindsey P, Wilson JA, Horvath R, Yu-Wai-Man P, Gorman GS, Taylor RW, Ng Y, McFarland R, Moore BC, Chinnery PF. Both mitochondrial DNA and mitonuclear gene mutations cause hearing loss through cochlear dysfunction. Brain. 2016 Jun;139(Pt 6):e33. Epub 2016 Mar 25. PMID: 27016405

1089. Martikainen MH, Ng YS, Gorman GS, Alston CL, Blakely EL, Schaefer AM, Chinnery PF, Burn DJ, Taylor RW, McFarland R, Turnbull DM. Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease. JAMA Neurol. 2016 Jun 1;73(6):668-74. PMID: 27111573

1090. Dombi E, Diot A, Morten K, Carver J, Lodge T, Fratter C, Ng YS, Liao C, Muir R, Blakely EL, Hargreaves I, Al-Dosary M, Sarkar G, Hickman SJ, Downes SM, Jayawant S, Yu-Wai-Man P, Taylor RW, Poulton J. The m.13051G>A mitochondrial DNA mutation results in variable neurology and activated mitophagy. Neurology. 2016 May 17;86(20):1921-3. Epub 2016 Apr 22. PMID: 27164671

1091. Metodiev MD, Thompson K, Alston CL, Morris AA, He L, Assouline Z, Rio M, Bahi-Buisson N, Pyle A, Griffin H, Siira S, Filipovska A, Munnich A, Chinnery PF, McFarland R, Rötig A, Taylor RW. Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies. Am J Hum Genet. 2016 May 5;98(5):993-1000. Epub 2016 Apr 28. PMID: 27132592

1092. Lewis-Smith D, Kamer KJ, Griffin H, Childs AM, Pysden K, Titov D, Duff J, Pyle A, Taylor RW, Yu-Wai-Man P, Ramesh V, Horvath R, Mootha VK, Chinnery PF. Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood. Neurol Genet. 2016 Mar 3;2(2):e59. eCollection 2016 Apr. PMID: 27123478

1093. Pisano A, Cerbelli B, Perli E, Pelullo M, Bargelli V, Preziuso C, Mancini M, He L, Bates MG, Lucena JR, Della Monica PL, Familiari G, Petrozza V, Nediani C, Taylor RW, d'Amati G, Giordano C. Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure. Cardiovasc Pathol. 2016 Mar-Apr;25(2):103-12. Epub 2015 Sep 30. PMID: 26764143

1094. Wilson IJ, Carling PJ, Alston CL, Floros VI, Pyle A, Hudson G, Sallevelt SC, Lamperti C, Carelli V, Bindoff LA, Samuels DC, Wonnapinij P, Zeviani M, Taylor RW, Smeets HJ, Horvath R, Chinnery PF. Mitochondrial DNA sequence characteristics modulate the size of the genetic bottleneck. Hum Mol Genet. 2016 Mar 1;25(5):1031-41. Epub 2016 Jan 5. PMID: 26740552

1095. Spiegel R, Saada A, Flannery PJ, Burté F, Soiferman D, Khayat M, Eisner V, Vladovski E, Taylor RW, Bindoff LA, Shaag A, Mandel H, Schuler-Furman O, Shalev SA, Elpeleg O, Yu-Wai-Man P. Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation. J Med Genet. 2016 Feb;53(2):127-31. Epub 2015 Nov 11. PMID: 26561570

1096. Kullar P, Alston CL, Ball S, Blakely EL, Differ AM, Fratter C, Sweeney MG, Taylor RW, Chinnery PF. The frequency of the m.1555A>G (MTRNR1) variant in UK patients with suspected mitochondrial deafness. Hearing Balance Commun. 2016;14(2):101-102. Epub 2016 May 20. PMID: 27257558

1097. Ferrer-Cortès X, Narbona J, Bujan N, Matalonga L, Del Toro M, Arranz JA,

108 | P a g e Riudor E, Garcia-Cazorla A, Jou C, O'Callaghan M, Pineda M, Montero R, Arias A, García-Villoria J, Alston CL, Taylor RW, Briones P, Ribes A, Tort F. A leaky splicing mutation in NFU1 is associated with a particular biochemical phenotype. Consequences for the diagnosis. Mitochondrion. 2016 Jan;26:72-80 Epub 2015 Dec 11. PMID: 26688339

Michael Trenell

1098. Bates MG, Newman JH, Jakovljevic DG, Hollingsworth KG, Alston CL, Zalewski P, Klawe JJ, Blamire AM, MacGowan GA, Keavney BD, Bourke JP, Schaefer A, McFarland R, Newton JL, Turnbull DM, Taylor RW, Trenell MI, Gorman GS. Defining cardiac adaptations and safety of endurance training in patients with m.3243A>G-related mitochondrial disease. Int J Cardiol. 2013 Oct 9;168(4):3599-608. PMID: 23742928

1099. Galna B, Newman J, Jakovljevic DG, Bates MG, Schaefer AM, McFarland R, Turnbull DM, Trenell MI, Gorman GS, Rochester L. Discrete gait characteristics are associated with m.3243A>G and m.8344A>G variants of mitochondrial disease and its pathological consequences. J Neurol. 2014 Jan;261(1):73-82. PMID: 24150688

1100. Gorman GS, Blakely EL, Hornig-Do HT, Tuppen HA, Greaves LC, He L, Baker A, Falkous G, Newman J, Trenell MI, Lecky B, Petty RK, Turnbull DM, McFarland R, Taylor RW. Novel MTND1 mutations cause isolated exercise intolerance, complex I deficiency and increased assembly factor expression. Clin Sci (Lond). 2015 Jun;128(12):895-904. PMID: 25626417

Patrick Chinnery

1101. Keogh MJ, Daud D, Chinnery PF. Exome sequencing: how to understand it. Practical Neurology 2013 Dec;13(6):399-407. PMID: 23727621

1102. Pyle A, Griffin H, Duff J, Bennett S, Zwolinski S, Smertenko T, Yu-Wai Man P, Santibanez-Koref M, Horvath R, Chinnery PF. Late-Onset Sacsinopathy Diagnosed by Exome Sequencing and Comparative Genomic Hybridization. Journal of Neurogenetics 2013 Dec;27(4):176-82 PMID: 24180463

1103. Fisher KM, Chinnery PF, Baker SN, Baker MR Enhanced reticulospinal output in patients with (REEP1) hereditary spastic paraplegia type 31. Journal of Neurology 2013 Dec;260(12):3182-4. PMID: 24221643

1104. Neeve VC, Pyle A, Boczonadi V, Gomez-Duran A, Griffin H, Santibanez-Koref M, Gaiser U, Bauer P, Tzschach A, Chinnery PF, Horvath R. Clinical and functional characterisation of the combined respiratory chain defect in two sisters due to autosomal recessive mutations in MTFMT. Mitochondrion 2013 Nov;13(6):743-8. PMID: 23499752

1105. Keogh M, Chinnery PF. Hereditary mtDNA heteroplasmy: a baseline for ageing? Cell Metabolism 2013 Oct 1;18(4):463-464. PMID: 24093673

1106. Yu-Wai-Man C, Smith FE, Firbank MJ, Guthrie G, Guthrie S, Gorman GS, Taylor RW, Turnbull DM, Griffiths PG, Blamire AM, Chinnery PF, Yu-Wai-Man P. Extraocular Muscle Atrophy and Central Nervous System Involvement in Chronic Progressive External Ophthalmoplegia. PLoS One 2013 Sep 27;8(9):e75048. PMID: 24086434

1107. *Pfeffer P, Horvath R, Klopstock T, Mootha VK, Suomalainen A, Koene S, Hirano M, Zeviani M, Bindoff LA, Yu-Wai-Man P, Hanna M, Carelli V, McFarland R, Majamaa K, Turnbull DM, Smeitink J, Chinnery PF. New treatments for mitochondrial disease—no time to drop our standard. Nature Reviews Neurology 2013 Aug;9(8):474-81. PMID: 23817350

109 | P a g e 1108. Yu-Wai-Man P, Chinnery PF. Dominant Optic Atrophy: Novel OPA1 Mutations and Revised Prevalence Estimates. Ophthalmology. 2013 Aug;120(8):1712-1712. PMID:23916084

1109. Keogh MJ, Morris CM, Chinnery PF. Neuroferritinopathy. International Reviews in Neurobiology 2013;110C:91-123. PMID: 24209436

1110. Pfeffer G, Burke A, Yu-Wai-Man P, D Alastair S Compston, Chinnery PF. The clinical features of MS associated with Leber hereditary optic neuropathy mtDNA mutations. Neurology 2013:10;81(24): 2073-81. PMID: 24198293

1101. Gardner K, Hall PA, Chinnery PF, Payne BA. HIV Treatment and Associated Mitochondrial Pathology: Review of 25 Years of in Vitro, Animal, and Human Studies. Toxicological Pathology 2013. PMID: 24067671

1102. Yu-Wai-Man P, Chinnery PF. Leber Hereditary Optic Neuropathy. 2000 Oct 26 [Updated 2013 Sep 19]. In: Pagon RA, Adam MP, Bird TD, et al., editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2013. http://www.ncbi.nlm.nih.gov/books/NBK1174/

1103. Spyropoulos A, Manford M, Horvath R, Alston CL, Yu-Wai-Man P1, He L-P, Taylor RW, Chinnery PF.Near identical segregation of mtDNA heteroplasmy in blood, muscle, urinary epithelium and hair follicles in twins with optic atrophy, ptosis and intractable epilepsy. JAMA Neurology 2013;70(12):1552-5. PMID: 24126373.

1104. Peall K, Smith DJ, Kurian M, Wardle M, Waite A, Hedderly T, Lin J, Smith M, Whone A, Pall H, White C, Lux A, Jardine P, Bajaj N, Lynch B, Kirov G, O'Riordan S, Samuel M, Lynch T, King M, Chinnery P, Warner T, Blake DJ, Owen M, Morris H. Are psychiatric symptoms a core phenotype of myoclonus dystonia syndrome caused by sgce mutations? Journal of Neurology Neurosurgery & Psychiatry 2013;84(9):e1. PMID: 23922421

1105. Chinnery PF. One complex world of mitochondrial parkinsonism Brain 2013 Aug;136(Pt 8):2336-41. PMID:23884808

1106. Bailie M, Votruba M, Griffiths PG, Chinnery PF, Yu-Wai-Man P. Visual and psychological morbidity among patients with autosomal dominant optic atrophy. Acta Ophthalmologica 2013 Aug;91(5):e413-4. PMID: 23452392

1107. Jaiser SR, Baker MR, Whittaker RG, Birchall D, Chinnery PF. Clinical Reasoning: A 39-year-old man with abdominal cramps. Neurology 2013 Jul 9;81(2):e5-9. PMID:23836948

1108. Boczonadi V, Smith PM, Pyle A, Gomez-Duran A, Schara U, Tulinius M, Chinnery PF, Horvath R. Altered 2-thiouridylation impairs mitochondrial translation in reversible infantile respiratory chain deficiency. Human Molecular Genetics 2013:22(22):4602-15. PMID:23814040

1109. Collerton J, Ashok D, Martin-Ruiz C, Pyle A, Hudson G, Yadegarfar M, Davies K, Jagger C, von Zglinicki T, Kirkwood TBL, Chinnery PF. Frailty and mortality are not influenced by mitochondrial DNA haplotypes in the very old. Neurobiology of Ageing 2013;34(12):2889.e1-4. PMID: 23639206

1110. Thouin A, Griffiths PG, Hudson G, Chinnery PF, Yu-Wai-Man P. Raised intraocular pressure as a potential risk factor for visual loss in Leber hereditary optic neuropathy. PLoS One 2013 May 7;8(5):e63446. PMID: 23667621

1111. Hackman P, Sarparanta J, Lehtinen S, Vihola A, Evilä A, Jonson PH, Luque H, Kere J, Screen M, Chinnery PF, Åhlberg G, Edström L, Udd B. Welander distal myopathy is

110 | P a g e caused by a mutation in the RNA- binding protein TIA1. Annals of Neurology 2013 Apr;73(4):500-9. PMID 23401021

1112. Hudson G, Chinnery PF. Mitochondrial genetics. British Medical Bulletin Br Med Bull. 2013;106:135-59. PMID: 23704099

1113. Yu-Wai-Man P, Chinnery PF. Reply: Sensorineural hearing loss in OPA1-linked disorders. Brain 2013 Feb 4. [Epub ahead of print] No abstract available. PMID: 23650221

1114. Keogh MJ, Chinnery PF. How to spot mitochondrial disease in adults. Clinical Medicine 2013 Feb;13(1):87-92. PMID: 23472503

1115. Samuels DC, Wonnapinij P, Chinnery PF. Preventing the transmission of pathogenic mitochondrial DNA mutations: can we achieve long-term benefits from germ-line gene transfer? Human Reproduction 2013:28(3):554-9. PMID: 23297368

1116. Bathgate D, Wigley R, Gorman G,, Horvath R, Chinnery PF. Childhood presentation of “adult” polyglucosan body disease: normal GBE1 sequence with no glycogen branching enzyme activity. Annals of Neurology 2013 Feb;73(2):317-8. PMID:23526558

1117. Hudson G, Panoutsopoulou K, Wilson I, Southam L, Rayner NW, Arden N, Birrell F, Carluke I, Carr A, Chapman K, Deloukas P, Doherty M, McCaskie A, Ollier WER, Ralston SH, Reed MR, Spector TD, Valdes AM, Wallis GA, Wilkinson JM, arcOGEN Consortium, Zeggini E, Samuels DC, Loughlin J, Chinnery PF. No evidence of an association between mitochondrial DNA variants and osteoarthritis in 7393 cases and 5122 controls. Annals of the Rheumatic Diseases 2013 Jan;72(1):136-9. PMID:22984172

1118. Keogh MJ, Singh B, Chinnery PF. Early neuropsychiatry features in neuroferritinopathy. Movement Disorders 2013;28:1310-1313. PMID: 23436236

1119. Peall KJ, Smith DJ, Kurian MA, Wardle M, Waite AJ, Hedderly T, Lin JP, Smith M, Whone A, Pall H, White C, Lux A, Jardine P, Bajaj N, Lynch B, Kirov G, O'Riordan S, Samuel M, Lynch T, King MD, Chinnery PF, Warner TT, Blake DJ, Owen MJ, Morris HR. SGCE mutations cause psychiatric disorders: clinical and genetic characterization. Brain 2013 Jan;136(Pt 1):294-303. PMID: 23365103

1120. Payne BAI, Wilson IJ, Yu-Wai-Man P, Coxhead J, Deehan D, Horvath R, Taylor RW, Samuels DC, Santibanez-Koref M, Chinnery PF. Universal heteroplasmy of human mitochondrial DNA. Human Molecular Genetics 2013 Jan 15;22(2):384-90. PMID:23077218.

1121. Klopstock T, Metz G, Yu-Wai-Man P, Büchner B, Gallenmüller C, Bailie M, Nwali N, Griffiths P.G, von Livonius B, Reznicek L, Rouleau J, Coppard N, Meier T, Chinnery PF. Persistence of the treatment effect of idebenone in Leber’s Hereditary Optic Neuropathy. Brain 2013 Feb;136(Pt 2):e230. PMID: 23388409

1122. Talim B, Pyle A, Griffin H, Topaloglu H, Tokatli A, Keogh MJ, Santibanez-Koref M, Chinnery PF, Horvath R. Multisystem fatal infantile disease caused by a novel homozygous EARS2 mutation. Brain 2013 Feb;136(Pt 2):e228. PMID:23008233.

1123. Pfeffer G, Pyle A, Griffin H, Miller J, Wilson V, Turnbull L, Fawcett K, Sim D, Eglon G, Hadjivassilio M, Horvath R, Németh A, Chinnery PF, SPG7 mutations are a common cause of undiagnosed ataxia. Neurology 2014. PMID: 25941202

1124. Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski- Feder E, Abicht A, Czermin B, Kleinle S, Morris AAM, Vassallo G, Gorman G, Ramesh V,

111 | P a g e Turnbull DM, Santibanez-Koref M, McFarland R, Horvath R, Chinnery PF. Use of whole exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiency. Journal of the American Medical Association 2014;312(1):68-77. PMID: 25058219

1125. Pyle A, Smertenko T, Bargiela D, Griffin H, Duff J, Appleton M, Douroudis K, Pfeffer G, Santibanez-Koref M, Eglon G, Yu-Wai-Man P, Ramesh V, Horvath R, Chinnery PF. Exome sequencing in undiagnosed inherited and sporadic ataxias. Brain 2014. PMID: 25497598

1126. Kopajtich R, Nicholls TJ, Rorbach J, Metodiev MD, Freisinger P, Mandel H, Vanlander A, Ghezzi D, Carrozzo R, Taylor RW, Marquard K, Murayama K, Wieland T, Schwarzmayr T, Mayr JA, Pearce SF, Powell CA, Saada A, Ohtake A, Invernizzi F, Lamantea E, Sommerville EW, Pyle A, Chinnery PF, Crushell E, Okazaki Y, Kohda M, Kishita Y, Tokuzawa Y, Assouline Z, Rio M, Feillet F, Mousson de Camaret B, Chretien D, Munnich A, Menten B, Sante T, Smet J, Régal L, Lorber A, Khoury A, Zeviani M, Strom TM, Meitinger T, Bertini ES, Van Coster R, Klopstock T, Rötig A, Haack TB, Minczuk M, Prokisch H. Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy. Am J Hum Genet. 2014 Dec 4;95(6):708-20. PMID: 25434004

1127. Nile DL, Brown AE, Kumaheri MA, Blair HR, Heggie A, Miwa S, Cree LM, Payne B, Chinnery PF, Brown L, Gunn DA, Walker M. Age-related mitochondrial DNA depletion and the impact on pancreatic Beta cell function. PLoS One. 2014 Dec 22;9(12):e115433. PMID: 25532126

1128. *Heckman MG, Schottlaender L, Soto-Ortolaza AI, Diehl NN, Rayaprolu S, Ogaki K, Fujioka S, Murray ME, Cheshire WP, Uitti RJ, Wszolek ZK, Farrer MJ, Sailer A, Singleton AB, Chinnery PF, Keogh MJ, Gentleman SM, Holton JL, Aoife K, Mann DM, Al-Sarraj S, Troakes C, Dickson DW, Houlden H, Ross OA. LRRK2 exonic variants and risk of multiple system atrophy. Neurology. 2014 Dec 9;83(24):2256-61. PMID: 25378673

1129. Dimitriadis K, Leonhardt M, Yu-Wai-Man P, Kirkman MA, Korsten A, De Coo IF, Chinnery PF, Klopstock T. Leber's hereditary optic neuropathy with late disease onset: clinical and molecular characteristics of 20 patients. Orphanet J Rare Dis. 2014 Oct 23;9:158. PubMed PMID: 25338955

1130. Herrmann DN, Horvath R, Sowden JE, Gonzales M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmüller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S.Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. American Journal of Human Genetics 2014 Sep 4;95(3):332-9. PMID:25192047

1131. Balreira A, Boczonadi V, Barca E, Pyle A, Bansagi B, Appleton M, Graham C, Hargreaves IP, Rasic VM, Lochmüller H, Griffin H, Taylor RW, Naini A, Chinnery PF, Hirano M, Quinzii CM, Horvath R ANO10 mutations cause ataxia and coenzyme Q10 deficiency. Journal of Neurology 2014 Sep 3. PMID:25182700

1132. Peall KJ, Kurian MA, Wardle M, Waite AJ, Hedderly T, Lin JP, Smith M, Whone A, Pall H, White C, Lux A, Jardine PE, Lynch B, Kirov G, O'Riordan S, Samuel M, Lynch T, King MD, Chinnery PF, Warner TT, Blake DJ, Owen MJ, Morris HR. SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype. Journal of Neurology 2014 Sep 11. [Epub ahead of print] PMID:25209853

1133. Yu-Wai-Man P, Chinnery PF. Reply: 'Behr syndrome' with OPA1 compound

112 | P a g e heterozygote mutations. Brain 2014 Aug 21. pii: awu235. [Epub ahead of print] PMID: 25146915

1134. Haghighi A, Haack TB, Atiq M, Mottaghi H, Haghighi-Kakhki H, Bashir RA, Ahting U, Feichtinger RG, Mayr JA, Rötig A, Lebre AS, Klopstock T, Dworschak A, Pulido N, Saeed MA, Saleh-Gohari N, Holzerova E, Chinnery PF, Taylor RW, Prokisch H. Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients. Orphanet J Rare Diseases 2014 Aug 20;9(1):119. PMID:25208612

1135. Chinnery PF. Mitochondrial Disorders Overview. 2000 Jun 8 [Updated 2014 Aug 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1224/

1136. Boczonadi V, Müller JS, Pyle A, Munkley J, Dor T, Quartararo J, Ferrero I, Karcagi V, Giunta M, Polvikoski T, Birchall D, Princzinger A, Cinnamon Y, Lützkendorf S, Piko H, Reza M, Florez L, Santibanez-Koref M, Griffin H, Schuelke M, Elpeleg O, Kalaydjieva L, Lochmüller H, Elliott DJ, Chinnery PF, Edvardson S, Horvath R. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nature Communications 2014 Jul 3;5:4287. PMID:24989451

1137. Griffin HR, Pyle A, Blakely EL, Alston CL, Duff J, Hudson G, Rita Horvath R, Wilson IJ, Santibanez-Koref M, Taylor RW, Chinnery PF. Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations. Genetics in Medicine 2014: PMID:24901348

1138. Yu-Wai-Man P, Chinnery PF. Reply: Early-onset Behr syndrome due to compound heterozygous mutations in OPA1. Brain 2014 Jul 10. pii: awu187. [Epub ahead of print] PMID:25012222

1139. Bargiela D, Eglon G, Horvath R, Chinnery PF. An Under-Recognised Cause of Spastic Paraparesis in Middle-Aged Women. Practical Neurology 2014 Jun;14(3):182-4. PMID: 24154795

1140. Whittaker RG, Chinnery PF, Miller JA. Teaching Video NeuroImages: Muscle cramps and a raised creatine kinase. Neurology 2014 Jun 17;82(24):e220-1. PMID 24960836

1141. Tzoulis C, Tuong Tran G, Coxhead J, Bertelsen B, Lilleng PK, Balafkan N, Payne B, Miletic H, Chinnery PF, Bindoff LA. The molecular pathogenesis of POLG-related neurodegeneration. Annals of Neurology 2014. PMID:24841123

1142. Yarham JW, Lamichhane TN, Pyle A, Mattijssen S, Baruffini E, Bruni F, Donnini C, Vassilev A, He L, Blakely EL, Griffin H, Santibanez-Koref M, Bindoff LA, Ferrero I, Chinnery PF, McFarland R, Maraia RJ, Taylor RW. Defective i6A37 Modification of Mitochondrial and Cytosolic tRNAs Results from Pathogenic Mutations in TRIT1 and its Substrate tRNA. PLoS Genetics 2014 Jun 5;10(6):e1004424. PMID:24901367

1143. Gorman GS, Pfeffer G, Griffin H, Blakely EL, Kurzawa-Akanbi M, Gabriel J, Sitarz K, Roberts M, Schoser B, Pyle A, Schaefer AM, McFarland R, Turnbull DM, Horvath R, Chinnery PF, Taylor RW. Clonal expansion of secondary mtDNA deletions associated with spinocerebellar ataxia type 28. JAMA Neurology 2014. PMID: 25420100

1144. Pyle A, Ramesh V, Bartsakoulia M, Boczonadi V, Gomez-Duran A. Herczegfalvi A, Blakely EL, Smertenko T, Duff J, Eglon G, Moore D, Yu Wai Man P, Douroudis K, Santibanez-Koref M, Griffin H, Lochmuller H, Karcagi V, Taylor RW, Chinnery PF,

113 | P a g e Horvath R. Behr’s Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in the C12orf65 Gene. Journal of Neuromuscular Disease 2014:1:55-63. PMID: 26380172

1155. Yu-Wai-Man P, Carelli V, Chinnery PF. 197th ENMC international workshop: Neuromuscular disorders of mitochondrial fusion and fission - OPA1 and MFN2 molecular mechanisms and therapeutic strategies: 26-28 April 2013, Naarden, The Netherlands. Neuromuscular Disorders 2014 May 21. PMID: 24928537

1156. Hudson G, Gomez-Duran A, Wilson IJ, Chinnery PF. Recent mitochondrial DNA mutations increase the risk of developing common late-onset human diseases. PLoS Genetics 2014:May 22;10(5):e1004369.eCollection 2014 May. PMID:24852434.

1157. Gardner K, Payne BAI, Horvath R, Chinnery PF. Use of stereotypical mutational motifs to define resolution limits for the ultra-deep resequencing of mitochondrial DNA. European Journal of Human Genetics 2014 PMID: 24896153

1158. Sitarz KS, Elliott HR, Karaman BS, Relton C, Chinnery PF, Horvath R. Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts. Molecular Genetics and Metabolism 2014. PMID:24725338

1159. Pfeffer G, Gorman GS, Griffin H, Kurzawa-Akanbi M, Blakely EL, Wilson I, Sitarz K, Moore D, Murphy JL, Alston CL, Pyle A, Coxhead J, Payne B, Gorrie GH, Longman C, Hadjivassiliou M, McConville J, Dick D, Imam I, Hilton D, Norwood F, Baker MR, Jaiser SR, Yu-Wai-Man P, Farrell M, McCarthy A, Lynch T, McFarland R, Schaefer AM, Turnbull DM, Horvath ,Taylor RW, Chinnery PF. Mutations in the spastic paraplegia 7 gene (SPG7) cause chronic progressive external ophthalmoplegia through disordered mtDNA maintenance. Brain 2014 May. 137 (Pt 5):1323-36. PMID:24727571

1160. Chinnery PF, Craven L, Mitalipov S, Stewart JB, Herbert M, Turnbull DM. The challenges of mitochondrial replacement. PLoS Genetics 2014: Apr 24;10(4):e1004315. PMID:24762741

1161. Chaouch A, Brennan KM, Hudson J, Longman C, McConville J, Morrison PJ, Farrugia ME, Petty R, Stewart W, Norwood F, Horvath R, Chinnery PF, Costigan D, Winer J, Polvikoski T, Healy E, Sarkozy A, Evangelista T, Pogoryelova O, Eagle M, Bushby K, Straub V, Lochmüller H. Two recurrent mutations are associated with GNE myopathy in the North of Britain. Journal of Neurology Neurosurgery & Psychiatry. 2014. PMID: 24695763.

1162. Yu-Wai-Man P, Votruba M, Moore AT, Chinnery PF. Treatment strategies for inherited optic neuropathies: past, present and future. Eye (Lond). 2014 Mar 7. PMID: 24603424

1163. Pfeffer G, Sambuughin N, Olivé M, Tyndel F, Toro C, Goldfarb LG, Chinnery PF.A new disease allele for the p.C30071R mutation in titin causing hereditary myopathy with early respiratory failure. Neuromuscular Disorders 2014 Mar;24(3):241-4. PMID: 24444549

1164. Pfeffer G, Barresi R, Wilson IJ, Hardy SA, Griffin H, Hudson J, Elliott HR, Ramesh AV, Radunovic A, Winer J, Vaidya S, Raman A, Busby M, Farrugia ME, Ming A, Everett C, Emsley HCA, Horvath R, Straub V, Bushby K, Lochmuller H, Chinnery PF, Sarkozy A. Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure. Journal of Neurology Neurosurgery & Psychiatry 2014 Mar;85(3):331-8. PMID: 23486992

1165. Wiley L, Ashok D, Martin-Ruiz C, Talbot DC, Collerton J, Kingston A, Davies K, Chinnery PF, Catt M, Jagger C, Kirkwood TB, von Zglinicki T. Reactive oxygen species production and mitochondrial dysfunction in white blood cells are not valid biomarkers of

114 | P a g e ageing in the very old. PLoS One 2014 Mar 10;9(3):e91005. eCollection 2014. PMID:24614678

1166. Pfeffer G, Chinnery PF. Hereditary Myopathy with Early Respiratory Failure (HMERF). In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K, editors. GeneReviews™ [Internet]. Seattle (WA): University of Washington, Seattle; 1993- 2014. 2014 Feb 27. PMID: 24575448

1167. Bulstrode H, Nicoll JA, Hudson G, Chinnery PF, Pietro VD, Belli A. Mitochondrial and traumatic brain injury. Annals of Neurology 2014;75:186-95. PMID: 24523223

1168. Pfeffer G, Joseph JT, Innes AM, Frizzell JB, Wilson IJ, Brownell AKW, Chinnery PF. Titinopathy in a Canadian family sharing the British founder haplotype. Canadian Journal of the Neurological Sciences 2014 Jan;41(1):90-4. PMID: 24384345

1169. Yu-Wai-Man P, Pyle A, Griffin H, Santibanez-Korev M, Horvath R, Chinnery PF. Abnormal retinal thickening is a common feature among patients with ARSACS-related phenotypes. British Journal of Ophthalmology 2014 Jan 23. PMID: 24457356

1170. Pfeffer G, Chinnery PF Reply to Lange et al: Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain. Brain 2014: PMID: 24578547

1171. Pfeffer G, Griffin H, Pyle A, Horvath R, Chinnery PF. Hereditary myopathy with early respiratory failure is caused by mutations affecting the titin FN3 119 domain. Brain 2014: 2014 Apr;137(Pt 4):e271. PMID: 24271327.

1172. Giordano C, Iommarini L, Giordano L, Maresca A, Pisano A, Valentino ML, Caporali L, Liguori R, Deceglie S, Roberti M, Fanelli F, Fracasso F, Ross-Cisneros FN, D'Adamo P, Hudson G, Pyle A, Yu-Wai-Man P, Chinnery PF, Zeviani M, Salomao SR, Berezovsky A, Belfort R Jr, Ventura DF, Moraes M, Moraes Filho M, Barboni P, Sadun F, De Negri A, Sadun AA, Tancredi A, Mancini M, d'Amati G, Loguercio Polosa P, Cantatore P, Carelli V. Efficient mitochondrial biogenesis drives incomplete penetrance in Leber's hereditary optic neuropathy. Brain. 2014 Feb;137(Pt 2):335-53. PMID:24369379

1173. Rochester L, Galna B, Lord S, Mhiripiri D, Eglon G, Chinnery PF. Gait impairment precedes clinical symptoms in spinocerebellar ataxia type 6. Movement Disorders 2014 Feb;29(2):252-5. PMID: 24301795

1174. Yu-Wai-Man P, Hudson G, Klopstock T, Chinnery PF. Reply: Parsing the differences in affected with LHON: genetic versus environmental triggers of disease conversion (letter). Brain 2015: Dec 10. pii: awv340. PMID: 26657167

74. Bargiela D, Shanmugarajah P, Lo C, Blakely E, Taylor R, Horvath R, Wharton S, Chinnery PF, Hadjivassiliou M. Mitochondrial pathology in progressive cerebellar ataxia. Cerebellum & Ataxias 2015 Dec 4;2:16. eCollection 2015. PMID: 26640698

75. Angebault C, Guichet PO, Talmat-Amar Y, Charif M, Gerber S, Fares-Taie L, Gueguen N, Halloy F, Moore D, Amati-Bonneau P, Manes G, Hebrard M, Bocquet B, Quiles M, Piro- Mégy C, Teigell M, Delettre C, Rossel M, Meunier I, Preising M, Lorenz B, Carelli V, Chinnery PF, Yu-Wai-Man P, Kaplan J, Roubertie A, Barakat A, Bonneau D, Reynier P, Rozet JM, Bomont P, Hamel CP, Lenaers G. Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies. American Journal of Human Genetics 2015 Nov 5;97(5):754-60. PMID: 26593267

115 | P a g e 1175. Chinnery PF. Mitochondrial disease in adults: what’s old and what’s new? EMBO Molecular Medicine 2015 Nov 26;7(12):1503-12. PMID: 26612854

1176. Stewart JB, Chinnery PF. The dynamics of mitochondrial DNA heteroplasmy: implications for human health and disease. Nature Reviews Genetics 2015 Aug 18;16(9):530-42. PMID: 26281784

1177. Keogh MJ, Aribisala BS, He J, Tulip E, Butteriss D, Morris C, Gorman G, Horvath R, Chinnery PF, Blamire AM. Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity. J Neurol. 2015 Jul 4. [Epub ahead of print] PMID: 26142024.

1178. Powell CA, Kopajtich R, D'Souza AR, Rorbach J, Kremer LS, Husain RA, Dallabona C, Donnini C, Alston CL, Griffin H, Pyle A, Chinnery PF, Strom TM, Meitinger T, Rodenburg RJ, Schottmann G, Schuelke M, Romain N, Haller RG, Ferrero I, Haack TB, Taylor RW, Prokisch H, Minczuk M. TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies. Am J Hum Genet. 2015 Jul 15. [Epub ahead of print] PMID: 26189817.

1179. Daud D, Griffin H, Douroudis K, Kleinle S, Eglon G, Pyle A, Chinnery PF, Horvath R. Whole exome sequencing and the clinician: we need clinical skills and functional validation in variant filtering. J Neurol. 2015 Jul;262(7):1673-7. PMID: 25957632.

1180. Horvath R, Lewis-Smith D, Douroudis K, Duff J, Keogh M, Pyle A, Fletcher N, Chinnery PF. SCP2 mutations and neurodegeneration with brain iron accumulation. Neurology 2015;85(21):1909-11. PMID: 26497993

1181. Tang WWC, Dietmann S, Irie N, Leitch HG, Floros VI, Hackett JA, Chinnery PF, Surani MA. A Unique of the Human Germline Resets the Epigenome for Development. Cell 2015; 161(6):1453-67. PMID: 26046444

1182. Keogh MJ, Aribisala BS, He J, Tulip E, Butteriss D, Morris C, Gorman G, Horvath R, Chinnery PF, Blamire AM. Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity. Journal of Neurology 2015;262(10):2232-40. PMID:26142024

1183. Martikainen MH, Chinnery PF. Mitochondrial disease: mimics and chameleons. Practical Neurology 2015;15(6):424-35. PMID: 26201977

1184. Halter JP, Schüpbach WMM, Mandel H, Casali C, Orchard K, Collin M, Valcarcel D, Rovelli A, Filosto M, Dotti MT, Marotta G, Pintos G, Barba P, Accarino A, Ferra C, Illa I, Beguin Y, Bakker JA, Boelens JJ, de Coo IFM, Fay K, Sue CM, Nachbaur D, Zoller H, Sobreira C, Pinto Simoes B, Hammans SR, Savage D, Martí R, Chinnery PF, Elhasid R, Gratwohl A, Hirano M. Allogeneic hematopoietic stem cell transplantation for mitochondrial neurogastrointestinal encephalomyopathy. Brain 2015; 138(Pt 10):2847-58. PMID: 2626451

1185. Powell CA, Kopajtich R, D’Souza A, Rorbach J, Kremer LS, Husain RA, Dallabona C, Donnini C, Alston CL, Griffin H, Pyle A, Chinnery PF, Strom TM, Meitinger T, Rodenburg RJ, Schottmann G, Schuelke M, Romain N, Haller R, Ferrero I, Haack TB, Taylor RW, Prokisch H, Minczuk M. Mutations in TRMT5 cause a defect in post-transcriptional modification of mitochondrial tRNA associated with multiple respiratory chain deficiencies. American Journal of Human Genetics 2015;97(2):319-28. PMID: 26189817

116 | P a g e 1186. Payne BA, Chinnery PF. Mitochondrial dysfunction in ageing: much progress but many unresolved questions. Biochim Biophys Acta 2015; 1847(11):1347-53. PMID:26050973

1187. Bansagi B. Griffin H, Ramesh V, Duff J, Pyle A, Chinnery PF, Horvath R. The p.Ser107Leu in BICD2 is a mutation ‘hot spot’ causing distal spinal muscular atrophy. Brain 2015; 138(Pt 11):e391. PMID:26063656

1188. Evangelista T, Bansagi B, Pyle A, Griffin H, Douroudis K, Polvikoski T, Antoniadi T, Bushby K, Straub V, Chinnery PF, Lochmüller H, Horvath R. Phenotypic variability of TRPV4 related neuropathies. Neuromuscul Disord. 2015 Jun;25(6):516-21.PMID: 25900305

1189. Payne BA, Gardner K, Blakely EL, Maddison P, Horvath R, Taylor RW, Chinnery PF. Clinical and pathological features of mitochondrial DNA deletion disease following antiretroviral treatment. JAMA Neurol. 2015 May;72(5):603-5 PMID: 25961175.

1190. Horvath R, Chinnery PF. Nuclear-mitochondrial proteins: too much to process? Brain. 2015 Jun;138(Pt 6):1451-3. PMID: 26013806.

1191. Tang WW, Dietmann S, Irie N, Leitch HG, Floros VI, Bradshaw CR, Hackett JA, Chinnery PF, Surani MA. A Unique Gene Regulatory Network Resets the Human Germline Epigenome for Development. Cell. 2015 Jun 4;161(6):1453-67. PMID: 26046444

1192. Payne BA, Chinnery PF. Mitochondrial dysfunction in aging: Much progress but many unresolved questions. Biochim Biophys Acta. 2015 Jun 4. pii: S0005-2728(15)00109-7 PMID: 26050973.

1193. Bansagi B, Griffin H, Ramesh V, Duff J, Pyle A, Chinnery PF, Horvath R. The p.Ser107Leu in BICD2 is a mutation 'hot spot' causing distal spinal muscular atrophy. Brain. 2015 Jun 10. [Epub ahead of print] PMID: 26063656.

1194. Pyle A, Hudson G, Wilson IJ, Coxhead J, Smertenko T, Herbert M, Santibanez-Koref M, Chinnery PF. Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans. PLoS Genet. 2015 May 14;11(5):e1005040. PMID: 25973765

1195. Keogh MJ, Steele H, Douroudis K, Pyle A, Duff J, Hussain R, Smertenko T, Griffin H, Santibanez-Koref M, Horvath R, Chinnery PF. Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia. J Neurol. 2015 May 16. [Epub ahead of print] PMID: 25976027.

1196. Keogh MJ, Chinnery PF. Mitochondrial DNA mutations in neurodegeneration. Biochim Biophys Acta. 2015 May 23. PMID: 26014345.

1197. Huemer M, Mulder-Bleile R, Burda P, Froese DS, Suormala T, Zeev BB, Chinnery PF, Dionisi-Vici C, Dobbelaere D, Gökcay G, Demirkol M, Häberle J, Lossos A, Mengel E, Morris AA, Niezen-Koning KE, Plecko B, Parini R, Rokicki D, Schiff M, Schimmel M, Sewell AC, Sperl W, Spiekerkoetter U, Steinmann B, Taddeucci G, Trejo-Gabriel-Galán JM, Trefz F, Tsuji M, Vilaseca MA, von Kleist-Retzow JC, Walker V, Zeman J, Baumgartner MR, Fowler B. Clinical pattern, mutations and in vitro residual activity in 33 patients with severe 5, 10 methylenetetrahydrofolate reductase (MTHFR) deficiency. J Inherit Metab Dis. 2015 May 30. [Epub ahead of print] PMID: 26025547.

1198. Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, Taylor RW, Turnbull DM, McFarland R. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015 May;77(5):753-9. PMID: 25652200.

117 | P a g e 1199. Pyle A, Nightingale HJ, Griffin H, Abicht A, Kirschner J, Baric I, Cuk M, Douroudis K, Feder L, Kratz M, Czermin B, Kleinle S, Santibanez-Koref M, Karcagi V, Holinski-Feder E, Chinnery PF, Horvath R. Respiratory chain deficiency in nonmitochondrial disease. Neurology Genetics 2015 Apr 27;1(1):e6. PMID: 27066545

1200. Keogh MJ, Pyle A, Daud D, Griffin H, Douroudis K, Eglon G, Miller J, Horvath R, Chinnery PF. Clinical heterogeneity of primary familial brain calcification due to a novel mutation in PDGFB. Neurology. 2015 Apr 28;84(17):1818-20. PMID: 25832657

1201. Pyle A, Griffin H, Keogh MJ, Horvath R, Chinnery PF. Reply: Evaluation of exome sequencing variation in undiagnosed ataxias. Brain. 2015 Apr 4. pii: awv088. [Epub ahead of print] PMID: 25842392

1202. Griffin H, Pyle A, Chinnery PF. Increased yield of exome sequencing by off-target mitochondrial DNA analysis. Ann Neurol. 2015 Mar;77(3):553. PMID: 25611826.

1203. Pfeffer G, Pyle A, Griffin H, Miller J, Wilson V, Turnbull L, Fawcett K, Sims D, Eglon G, Hadjivassiliou M, Horvath R, Németh A, Chinnery PF. SPG7 mutations are a common cause of undiagnosed ataxia. Neurology. 2015 Mar 17;84(11):1174-6. PMID: 25681447

1204. Horvath R, Chinnery PF. Modifying mitochondrial tRNAs: delivering what the cell needs. Cell Metab. 2015 Mar 3;21(3):351-2. PMID: 25738451.

1205. Euro L, Konovalova S, Asin-Cayuela J, Tulinius M, Griffin H, Horvath R, Taylor RW, Chinnery PF, Schara U, Thorburn DR, Suomalainen A, Chihade J, Tyynismaa H. Structural modeling of tissue-specific mitochondrial alanyl-tRNA synthetase (AARS2) defects predicts differential effects on aminoacylation. Front Genet. 2015 Feb 6;6:21. PMID: 25705216

1206. Gorman GS, Grady JP, Ng Y, Schaefer AM, McNally RJ, Chinnery PF, Yu-Wai-Man P, Herbert M, Taylor RW, McFarland R, Turnbull DM. Mitochondrial donation—how many women could benefit? N Engl J Med. 2015 Feb 26;372(9):885-7. PMID: 25629662.

1207. Pyle A, Smertenko T, Bargiela D, Griffin H, Duff J, Appleton M, Douroudis K, Pfeffer G, Santibanez-Koref M, Eglon G, Yu-Wai-Man P, Ramesh V, Horvath R, Chinnery PF. Exome sequencing in undiagnosed inherited and sporadic ataxias. Brain. 2015 Feb;138(Pt 2):276-83. PMID: 25497598

1208. Gorman GS, Pfeffer G, Griffin H, Blakely EL, Kurzawa-Akanbi M, Gabriel J, Sitarz K, Roberts M, Schoser B, Pyle A, Schaefer AM, McFarland R, Turnbull DM, Horvath R, Chinnery PF, Taylor RW. Clonal expansion of secondary mitochondrial DNA deletions associated with spinocerebellar ataxia type 28. JAMA Neurol. 2015 Jan;72(1):106-11. PMID: 25420100.

1209. Payne BA, Gardner K, Coxhead J, Chinnery PF. Deep resequencing of mitochondrial DNA. Methods Mol Biol. 2015;1264:59-66. PMID: 25631003.

1210. Payne BA, Cree L, Chinnery PF. Single-cell analysis of mitochondrial DNA. Methods Mol Biol. 2015;1264:67-76. PMID: 25631004.

1211. Burté F, Carelli V, Chinnery PF, Yu-Wai-Man P. Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat Rev Neurol. 2015 Jan;11(1):11-24. PMID: 25486875.

1212. Steele HE, Harris E, Barresi R, Marsh J, Beattie A, Bourke JP, Straub V, Chinnery PF. Cardiac involvement in hereditary myopathy with early respiratory failure: A cohort study. Neurology. 2016 Aug 10. [Epub ahead of print]. PMID: 27511179

118 | P a g e 1213. Majander A, Bitner-Glindzicz M, Chan CM, Duncan HJ, Chinnery PF, Subash M, Keane PA, Webster AR, Moore AT, Michaelides M, Yu-Wai-Man P. Lamination of the outer plexiform layer in optic atrophy caused by dominant WFS1 mutations. Ophthalmology 2016 PMID: 26875006

1214. Kullar PJ, Quail J, Lindsey P, Wilson JA, Horvath R, Yu-Wai-Man P, Moore BCJ, Chinnery PF. Both mitochondrial DNA and mitonuclear gene mutations cause hearing loss through cochlear dysfunction. Brain 2016 PMID: 27016405

1215. Nightingale H, Pfeffer G, Bargiela D, Horvath R, Chinnery PF. Emerging therapies for mitochondrial disorders. Brain 2016: PMID: 27190030

1216. Yu-Wai-Man P, Chinnery PF. Leber Hereditary Optic Neuropathy. 2000 Oct 26 [Updated 2016 Jun 23]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. http://www.ncbi.nlm.nih.gov/books/NBK1174/

1217. Olsen RK, Koňaříková E, Giancaspero TA, Mosegaard S, Boczonadi V, Mataković L, Veauville-Merllié A, Terrile C, Schwarzmayr T, Haack TB, Auranen M, Leone P, Galluccio M, Imbard A, Gutierrez-Rios P, Palmfeldt J, Graf E, Vianey-Saban C, Oppenheim M, Schiff M, Pichard S, Rigal O, Pyle A, Chinnery PF, Konstantopoulou V, Möslinger D, Feichtinger RG, Talim B, Topaloglu H, Coskun T, Gucer S, Botta A, Pegoraro E, Malena A, Vergani L, Mazzà D, Zollino M, Ghezzi D, Acquaviva C, Tyni T, Boneh A, Meitinger T, Strom TM, Gregersen N, Mayr JA, Horvath R, Barile M, Prokisch H. Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency. American Journal of Human Genetics 2016 Jun 2;98(6):1130- 1145. PMID: 27259049

1218. Metodiev MD, Thompson K, Alston CL, Morris AA, He L, Assouline Z, Rio M, Bahi- Buisson N, Pyle A, Griffin H, Siira S, Filipovska A, Munnich A, Chinnery PF, McFarland R, Rötig A, Taylor RW. Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies. American Journal of Human Genetics 2016 Apr 26. PMID: 27132592

1219. Martikainen MH, Ng YS, Gorman GS, Alston CL, Blakely EL, Schaefer AM, Chinnery PF, Burn DJ, Taylor RW, McFarland R, Turnbull DM. Clinical, Genetic, and Radiological Features of Extrapyramidal Movement Disorders in Mitochondrial Disease. JAMA Neurology 2016 Apr 25. PMID: 27111573

1220. Buret L, Rebillard G, Brun E, Angebault C, Pequignot M, Lenoir M, Do-Cruzeiro M, Tournier E, Cornille K, Saleur A, Gueguen N, Reynier P, Amati-Bonneau P, Barakat A, Blanchet C, Chinnery P, Yu-Wai-Man P, Kaplan J, Roux AF, Van Camp G, Wissinger B, Boespflug-Tanguy O, Giraudet F, Puel JL, Lenaers G, Hamel C, Delprat B, Delettre C. Loss of function of Ywhah in mice induces deafness and cochlear outer hair cells' degeneration. Cell Death Discovery 2016 Mar 7;2:16017. PMID: 27275396

1221. Lewis-Smith D, Kamer KJ, Griffin H, Childs A-M, Pysden K, Titov D, Duff J, Pyle A, Taylor RW, Yu-Wai-Man P, Ramesh V, Horvath R, Mootha VK, Chinnery PF. Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood. Neurology Genetics 2016: 2016 Mar 3;2(2):e59. PMID: 2712347

1222. *Wilson IJ, Carling PJ, Alston CL, Floros VI, Pyle A, Hudson G, Sallevelt SCEH, Lamperti C, Carelli V, Bindoff LA, Samuels DC, Wonnapinij P, Zeviani M, Taylor RW, Smeets HJM, Horvath R, Chinnery PF. Mitochondrial DNA Sequence Characteristics Modulate the Size of the Genetic Bottleneck. Human Molecular Genetics 2016: 2016 Mar

119 | P a g e 1;25(5):1031-41. PMID: 26740552

1223. Shen L, Diroma MA, Gonzalez M, Navarro-Gomez D, Leipzig J, Lott MT, van Oven M, Wallace DC, Muraresku CC, Zolkipli-Cunningham Z, Chinnery PF, Attimonelli M, Zuchner S, Falk MJ, Gai X. MSeqDR: A Centralized Knowledge Repository and Bioinformatics Web Resource to Facilitate Genomic Investigations in Mitochondrial Disease. Human Mutation 2016 Feb 26. PMID: 26919060

1224. Huemer M, Mulder-Bleile R, Burda P, Froese DS, Suormala T, Ben Zeev B, Chinnery PF, Dionisi-Vici C, Dobbelaere D, Gökcay G, Häberle J, Lossos A, Mengel E, Morris A, Niezen-Koning KE, Plecko B, Parini R, Rokicki D, Schiff M, Schimmel M, Sewell A, Sperl W, Spiekerkötter U, Steinmann B, Tadeucci G, Trejo J, Trefz F, Tsuji M , Vilaseca MA, von Kleist-Retzow J-C, Walker V, Zeman J, Baumgartner MR, Fowler D. Clinical pattern, mutations and in vitro residual activity in 33 patients with severe 5, 10 methylenetetrahydrofolate reductase (MTHFR) deficiency. Journal of Inherited Metabolic Disease 2016; 39(1):115-24. PMID:26025547

1225. Kullar P, Alston CL, Ball S, Blakely EL, Differ AM, Fratter C, Sweeney MG, Taylor RW, Chinnery PF. The frequency of the m.1555A>G (MTRNR1) variant in UK patients with suspected mitochondrial deafness. Hearing Balance Communication 2016;14(2):101-102. PMID: 27257558

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Appendix 5. Host support letters and Scientific Advisory Board membership and reports

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UCL FACULTY OF BRAIN SCIENCES FACULTY OFFICE

Dr Catherine Moody Programme Manager for Neurodegenerative Diseases Medical Research Council 14th floor One Kemble Street London WC2B 4AN

7th October 2016

Dear Catherine,

Re MRC Centre Mid-term report and future plans

I am writing to confirm UCL’s strongest support for the MRC Centre and the future vision as outlined in Professor Hanna’s mid-term report. There can be little doubt that the MRC Centre has had a genuinely transformational effect on advancing knowledge and breaking down translational barriers for patients with neuromuscular diseases.

The partnership between UCL and Newcastle has been impressively successful and has underpinned the creation of an effective experimental medicine platform that has delivered many natural history studies and experimental trials.

This partnership is of national importance for this area of neuroscience and is internationally leading as confirmed by Dr Griggs (chair of the SAB) letter.

UCL is committed to this area of Neuroscience and has invested significantly in recent years to further strengthen the work of the MRC Centre. This includes over £24m in new salaries and direct costs since 2008. Recruitments include Francesco Muntoni and Jenny Morgan in 2009; more recently Thomas Voit has joined us from the Institute of Myology Paris and Gipi Schiavo from CRUK. There are also notable recruits in Newcastle including Avan Sayer.

The critical mass of paediatric and adult expertise in this area at UCL is now one of the strongest in the world and when combined with the expertise in Newcastle is truly world leading. Indeed, in each University, steps have been taken to establish Neuromuscular Disease research fully in the departmental structure. In Newcastle the John Walton Centre for Muscular Dystrophy has been established; in UCL a new Department of Neuromuscular Disease will be established.

UCL School of Life and Medical Sciences, 1A Maple House, 149 Tottenham Court Road, London W1T 7NF Tel: +44 (0)20 7679 6924 Email: [email protected] Fax: +44 (0)20 7679 0876 http://www.ucl.ac.uk/brain-sciences

During the life of the MRC Centre, and partly as a result of its contribution, the field has advanced very rapidly indeed. Most genes have now been discovered (41 by the MRC Centre in the last 3 years) and clear targets for therapy identified. Neuromuscular Diseases is one area of neuroscience where translation to new therapies is realistic in the next 5 years. MRC Centre investigators have started to lead therapy development with successful FDA licensing of gene therapy in Duchenne and repurposing in channelopathies. The potential of this group to bring their expertise to the development of new therapies across a much wider range of neuromuscular diseases is now clear, and with the right support they are poised to be world leading and to have major impact in therapy development.

Importantly, UCL has made a recent major investment in drug discovery capability [over £12m, including a £10m award from ARUK direct costs and space] by establishing the ARUK UCL Drug Discovery Institute to pursue therapies for Dementia. However, the critical mass of drug discovery capability including medicinal chemistry represents a major opportunity to develop neuromuscular disease therapies with additional appropriate investment to enable connectivity.

UCL therefore fully endorses the vision outlined in the mid-term report and strongly supported by the MRC Centre international SAB to establish a radical new centre. The new centre will create new core capabilities in preclinical modelling (IPSc/gene editing), in drug discovery, in advanced biomarker programmes and in bioinformatics capability that will enable progress to therapies across many neuromuscular disease targets. Such a new centre would sit alongside the successful platforms established by the current Centre and which would no longer be funded by the MRC. It would undoubtedly also be a beacon of excellence for translational PhD training.

Furthermore, developing new therapies through experimental medicine is a major part of the Faculty of Brain Sciences strategic plan and complements the recently renewed Great Ormond Street and UCLH Biomedical Research Centres.

The MRC Centre team are clearly poised to make major progress to therapies over the next five years and UCL will very strongly support pursuing this vision in partnership with the MRC in a new Centre.

Yours sincerely

PROFESSOR ALAN THOMPSON FMEDSCI, FRCP, FRCPI DEAN, UCL FACULTY OF BRAIN SCIENCES

List of SAB meetings

14th Nov 2014 (report below)

21 Nov 2011

20th Nov 2009

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SAB Report

Report from SAB meeting 2014

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SAB membership

Robert Griggs

Professor of Neurology, Medicine, Pathology and Laboratory Medicine and Pediatrics at the University of Rochester School of Medicine and Dentistry. Chair of the Department of Neurology and Neurologist-in-Chief at Strong Memorial Hospital 1986-2008. President of the American Academy of Neurology (2009-2011).

Dr. Griggs is an internist/neurologist specialising in neuromuscular diseases with a focus on experimental therapeutics. He has directed an NIH-funded training programme in the Experimental Therapeutics of Neurological Disease since 1989. He has published over 400 scientific papers and 26 texts which span the fields of medicine and neurology. He served as President of the Association of University Professor of Neurology (1994-1996). He has served on the Council of the American Neurological Association. He served as Editor-in-Chief of Neurology (1997-2007). He is Neurology Editor of Cecil Textbook of Medicine and an Editor of Cecil Essentials of Medicine. Dr. Griggs has received numerous awards for teaching including the American Academy of Neurology A.B. Baker Award and Lecture for Excellence in Teaching. He directed the educational programs of the AAN from 1992-1997. In 1998 he received the Robert Wartenberg Award and Lectureship of the AAN. In 2004 he delivered the Soriano Lectureship of the American Neurological Association. He was elected to the National Academy of Medicine in 1998.

Dr. Griggs established and chaired the Executive Committee of the Muscle Study Group (MSG) (1998-2015), an international consortium of investigators focused on developing new treatments for neuromuscular disease. The MSG (http://www.urmc.rochester.edu/msg) is supported by grants from the National Institute of Health, industry, and a number of foundations. Dr. Griggs serves on the Board of Directors of the American Society for NeuroTherapeutics (ASENT) and on the Editorial Board of NeuroTherapeutics. Dr. Griggs’ grants are focused on developing treatments for neuromuscular channelopathies and muscular dystrophies.

Rick J. Barohn

Chairman, Department of Neurology, Gertrude and Dewey Ziegler Professor of Neurology University Distinguished Professor, Vice Chancellor for Research, President, KUMC Research Institute, University of Kansas Medical Center

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Dr. Richard J. Barohn is Chairman of the Department of Neurology and Vice Chancellor for Research at the University of Kansas Medical Center in Kansas City. He is also the Gertrude and Dewey Ziegler Professor of Neurology, and University Distinguished Professor, and the President of the Research Institute.

Dr. Barohn has served on the national medical advisory boards for the Myasthenia Gravis Foundation and the Guillain-Barre Syndrome Foundation International and The Myositis Association. He was the recipient of the 2000 Alumni Achievement Award for Medicine from the University of Missouri - Kansas City and the University of Kansas Chancellor’s Club Research Award in 2012. He became a KU University Distinguished Professor in 2014. He was appointed Vice Chancellor for Research for KUMC and President of the Research Institute. In this role he is the chief administrator for all KUMC grants, and he controls over 120 million dollars annually of research funds.

As chair of the Department of Neurology at KUMC, he also serves as the CEO of Kansas University Neurological Foundation and manages a financial portfolio that involves research and clinical revenue of more than $20 million annually.

His present research focuses on myopathies (such as polymyositis and muscular dystrophy), motor neuron disease (such as amyotrophic lateral sclerosis), peripheral neuropathies, and myasthenia gravis. He has developed a number of endpoint scales in neuromuscular disease that have been used in many clinical trials. He was the lead principal investigator of the multi-center study of mexiletine in nondystrophic myotonia that was published in JAMA. He has led or leads several multicenter international trials (methotrexate for myasthenia gravis, rasagiline for ALS, memantine for ALS and arimoclomol for IBM). He leads a 40 site comparative effectiveness study of drugs for painful neuropathy funded by PCORI and he is the leader of the rare disease program in the Greater Plains Collaborative PCORnet. He is the principal investigator on the NIH Clinical and Translational Science Award and the NeuroNEXT grant at KUMC. He is the Director of Frontiers: The Heartland Institute for Clinical and Translational Research. He has served on the editorial board for Neurology and is the Associate Editor for the Journal of Clinical Neuromuscular Disorders. He was the Founding Chair of the Section of Neuromuscular Disease in the American Academy of Neurology.

Eric P. Hoffman

Director of the Center for Genetic Medicine Research at Children’s National Medical Center Professor and Chair of the Department of Integrative at George Washington University, Washington DC

Dr. Hoffman is a human geneticist and translational researcher focused on neuromuscular disease, and skeletal muscle tissue in health and disease. His most recent efforts focus on drug development and clinical trials in Duchenne muscular dystrophy. He received his PhD in Drosophila molecular genetics from Johns Hopkins University, then carried out a post-doctoral fellowship at Boston Children’s Hospital and Harvard Medical School working on the identification of the DMD gene and protein. His current academic positions are Associate Dean for Research, School of

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Pharmacy and Pharmaceutical Sciences, Binghamton University – SUNY, where he is building a research program focused on facilitating drug development at the academic/industry interface. In the private sector, he is co-founder and CEO of ReveraGen Biopharma, co-founder and Vice President of AGADA Biosciences, and co-founder and President of TRiNDS LLC. He serves on Scientific Advisory Boards of Foundation to Eradicate Duchenne, CureDuchenne Foundation, C3 Foundation, Save Our Sons Foundation, and Duchenne UK. Research accomplishments include identification of the dystrophin protein, and defining its deficiency in DMD patient muscle, mdx mouse, dog and cat models. His lab identified initial voltage sensitive ion channel mutations in human disease, and genetic causes of recurrent pregnancy loss. He is an inventor on nine patents, and has authored over 500 publications.

Dr John Porter

Chief Science Officer Myotonic Dystrophy Foundation

Dr. Porter is Chief Science Officer for the Myotonic Dystrophy Foundation (MDF). He leads the development and implementation of the Foundation’s drug development and research agenda while positioning MDF as a knowledge center and resource for myotonic dystrophy care and treatment development science.

Over his academic research career (1983-2004), Dr. Porter ran an NIH- and foundation-funded research program focusing on extraocular muscle biology in health and disease, including the mechanisms responsible for its novel responses to a variety of neuromuscular disorders. While at the U.S. National Institutes of Health (NINDS/NIH), from 2004-2014, he managed research grant funding that included diseases affecting the motoneuron, neuromuscular junction, nerve, and skeletal muscle. During this time he helped facilitate team science and partnerships across academia, biotech and pharmaceutical companies, advocacy groups, and government, to foster translational research in neuromuscular disorders. Dr. Porter also helped advance rigorous design, implementation, and analysis of preclinical therapy development studies, a focus now well- engrained in NIH grant review standards. He also has served as CEO for Parent Project Muscular Dystrophy, a Duchenne patient advocacy organization.

Dr. Porter served a 10-year term as Executive Secretary for the interagency Muscular Dystrophy Coordinating Committee and has served on advisory boards for a variety of companies, publishers, foundations, government agencies, and academic organizations. He continues to consult for neuromuscular disease research and development organizations and companies.

Louis Ptacek

Distinguished Professor, Department of Neurology University of California, San Francisco

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Dr. Ptácek is the Coleman Distinguished Professor of Neurology. He is a neurologist, human geneticist, and cell and molecular neuroscientist at UCSF. His laboratory focuses on genetic diseases of muscle, heart and brain and hereditary variation of human sleep behavior. His group has cloned genes causing many disease and behavioral phenotypes in humans.

In addition, he and collaborators probe normal function of the encoded proteins in nervous system and pathophysiology of mutant proteins in human diseases using cellular electrophysiology, biochemistry, cell biology and animal modeling. Study of these single gene disorders is offering clues to susceptibility genes that may contribute to 'risk' of more common and genetically complex phenotypes like epilepsy, migraine, and normal sleep variation in the population.

One focus of his work is episodic neurological diseases. He pioneered the field of ‘Channelopathies’ that began with the mapping and cloning of a number of genes causing periodic paralysis and non- dystrophic myotonias, symptoms that he proposed as a model for other electrical disorders such as epilepsy, and migraine.

He and collaborators identified and characterized the first human families with a Mendelian circadian rhythm variant. These individuals have an extreme "morning lark" phenotype. His group and that of Ying-Hui Fu have gone from the clinical and physiologic characterization of this phenotype to the mapping and cloning of causative genes, biochemical study of the encoded proteins, and generation of animal models. They have collected many families with FASPS and these are being studied to identify additional human circadian rhythm genes. This work represents a move from purely ‘disease genetics’ to the genetics of human behavior.

Insights into the proteins causing these disorders and traits will ultimately lead to new insights into the normal function of the human nervous system and mechanisms of disease. Ultimately, such insights will lead to new therapies for treating patients with various neurological disorders.

Ptacek has been elected to the American Academy of Arts and Sciences, the National Academy of Medicine, and the National Academy of Sciences.

Mike Shy

Professor of Neurology, Pediatrics and Physiology Director of CMT Program Co-Director of Neuromuscular Division Co-Director of Neurogenetics Carver College of Medicine, University of Iowa

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Michael Shy is an internationally recognized expert in the inherited peripheral neuropathies collectively known as Charcot Marie Tooth disease (CMT). He received his BA at the University of Pennsylvania and his MD from Albany Medical College in Albany New York.

Dr. Shy did his Neurology training and a fellowship at the Neurological Institute of the Columbia Presbyterian Medical Center in New York City.

He was previously on the faculty of the Thomas Jefferson University in Philadelphia prior to Wayne State University in 1994, and moved to the University of Iowa in 2012. Dr Shy’s research is funded by the National Institutes of Health, the Muscular Dystrophy Association and the Charcot Marie Tooth Association.

Dr. Shy serves as the Chair of the Scientific Advisory Board of the Charcot Marie Tooth Association (CMTA) and also co-chairs the Star initiative of the CMTA that is directed towards identifying novel therapies for various forms of CMT. Dr. Shy serves on the Medical Advisory Board of the Muscular Dystrophy Association and also on the national committee of the MDA to develop transitional care for children developing into adulthood with neuromuscular disease.

Dr. Shy directs the NIH supported Rare Disease Clinical Research Consortium (RDCRC) on inherited neuropathies. He is also PI of the North American CMT Network, supprted by the MDA and CMTA and previously served as President of the Peripheral Nerve Society (PNS). He has published more than 100 articles, chapters and reviews, particularly on the inherited neuropathies.

Vincent Timmerman

Peripheral Neuropathy VIB Department of Molecular Genetics, University of Antwerp

The peripheral nervous system (PNS) exchanges motor, sensory and autonomic information between the central nervous system (CNS) and the limbs, organs and tissues. A series of biological and environmental conditions, such as genetic mutations, chemical stress, infections or metabolic insults, can lead to axonal loss and demyelination, the pathological hallmarks of peripheral nerve degeneration. Moreover, degeneration of peripheral nerves is accompanied by a local activation of the immune system.

The Peripheral Neuropathy Group aims at understanding the delicate balance between peripheral nerve homeostasis and degeneration by using two paradigms: 1. How do genetic mutations lead to peripheral nerve degeneration, and 2. What is the role of the innate immune system in nerve protection?

Inherited peripheral neuropathies (IPN) are caused by a length-dependent degeneration of peripheral nerves, resulting in progressive weakness in the limbs, wasting of foot and hand muscles as well as distal sensory loss. Charcot-Marie-Tooth (CMT) disease is the most common IPN with a prevalence of 1/2500. Over the years, our lab has become one of the main CMT research centers in the world; overall, 1/4 of the 60 IPN disease causing genes were found within our team or via

17 | P a g e international collaborations. Not surprisingly, many of these genes encode proteins that are involved in myelination and maintenance of the peripheral nerve. However, also ubiquitously expressed genes with basic tasks in every cell were found to specifically cause peripheral nerve degeneration.

Since the identification of a disease-associated gene is only a first step in unravelling the disease pathomechanism, we wanted to go further and aim to understand the functional consequences of the pathogenic mutations. We chose to focus on ubiquitously expressed genes that our lab identified to be causative for CMT. We aim to unravel the unique properties of these proteins in peripheral nerve biology as well as explore how these properties are affected upon mutation. To this end, we developed cellular (sensory and motor neurons or Schwann cells) and animal model systems. We are not only investigating the impact of disease-causing mutations on the well- established functions of these proteins, but additionally try to identify novel (potentially neurospecific) pathways in which these proteins might be involved by undertaking large scale approaches. Our ‘gene-driven’ approach is further complemented by a second research line, which aims to identify the role of the innate immune system in neuroprotection and -degeneration. Understanding how this balance is controlled might allow us to fine-tune or even stimulate an inherent neuroprotective response.

We strongly believe that our research strategy can contribute to the development of novel treatment strategies for CMT patients. The on-site interaction between neurologists, molecular geneticists and cell biologists places our lab in a privileged position: it ensures access to patient material, and also allows us to couple back our findings in the lab with clinical data. We also maintain contacts with the International CMT Consortium by co-organising meetings and workshops.

Biography

PhD: Univ. of Antwerp, Antwerp, Belgium, 1993 VIB Group leader since 1999 Associate Professor, Univ. of Antwerp since 2002 Professor, Univ. of Antwerp since 2008 Full Professor, University of Antwerp since 2012

Silvère van der Maarel

Head of Department of Human Genetics Leiden University Medical Center – LUMC, The Netherlands

Prof. Dr. Ir. Silvère van der Maarel was trained as a Human Geneticist at the Radboud University Nijmegen Medical Centerin the Netherlands. He continued to work on the positional cloning of X- linked disease genes at the Max Planck Institute of Molecular Biology in Berlin,Germany. In 1997, Silvère van der Maarel joined the Department of Human Genetics in Leiden(LUMC, the Netherlands). In 2006, he was appointed Professor of Medical Epigenetics and from 2012 he is chairing the Department of Human Genetics at the LUMC.

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Prof. van der Maarel’s scientific interests focus on the genetic and epigenetic regulation of repetitive DNA in the human genome in relation to disease. His main interest is the genetic and epigenetic basis of facioscapulohumeral muscular dystrophy (FSHD), an adult muscle disease caused by genetic and epigenetic changes in a repetitive DNA structure on the tip of the long arm of chromosome 4. He also made contributions to other muscular dystrophies including OPMD and LGMD.

Leiden University Medical Center (LUMC) Department of Human Genetics [email protected] LUMC Human Genetics LUMC Prof. S.M. van der Maarel

Steve Waxman

Bridget Marie Flaherty Professor of Neurology, Neurobiology and Pharmacology; Director, Center for Neuroscience & Regeneration/Neurorehabilitation Research; Yale University School of Medicine & VA Connecticut

Stephen Waxman, M.D., Ph.D. exemplifies the bridge between basic research and clinical medicine. He is the Bridget Marie Flaherty Professor of Neurology, Neurobiology, and Pharmacology at Yale University and is the Director of the Neuroscience and Regeneration Research Center, a multidisciplinary research institute established collaboratively by Yale University, the Department of Veterans Affairs, and the Paralyzed Veterans of America. Dr. Waxman served as Chairman of Neurology at Yale from 1986 until 2009. He is also Visiting Professor at University College London and the Institute of Neurology, London. He is Co-Director of the Yale-London Collaboration on CNS Repair.

Dr. Waxman received his BA from Harvard, and his MD and PhD degrees (1970, 1972) from Albert Einstein College of Medicine. Following Neurology Residency at Boston City Hospital/Harvard Medical School (1972-75), he held faculty appointments at Harvard Medical School, MIT, and Stanford University, prior to moving to Yale in 1986. Dr. Waxman has received international recognition for his research, which focuses molecular techniques on the nervous system, with the goal of finding new therapies that will promote recovery of function after injury to the brain, spinal cord, and peripheral nerves.

Dr. Waxman has published more than 600 scientific papers, has authored the clinical text Spinal Cord Compression, and has edited eight books. He has served on the editorial boards of many journals including Brain, Annals of Neurology, Trends in Neurosciences, Nature Clinical Neurology, and Trends in Molecular Medicine, and he serves as Editor of The Journal of Physiology and as Editor-in-Chief of Neuroscience Letters. Dr. Waxman has trained more than one hundred and fifty academic neurologists and neuroscientists who work at institutions around the world.

A member of the Institute of Medicine of the National Academy of Sciences, Dr. Waxman’s many awards include the Tuve Award from NIH, the Distinguished Alumnus Award from Albert Einstein

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College of Medicine, the Reingold Award from the National MS Society, and the Dystel Prize and the Wartenberg Award from the American Academy of Neurology, and the Soriano Award from the American Neurological Association.

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Appendix 6. Training report and list of current Centre students, project title, supervisor and funding

MRC Centre PhD and Education Programme UCL Lead: Mary Reilly, NCL Lead: Rita Horvath

The cornerstone of our training programme is our MRC Centre non-clinical and clinical PhD programme where all PhDs undertaken, whether clinical or non-clinical, are aligned with our five MRC Centre key disease themes.

4 year non-clinical PhD programme UCL: In UCL for the first year, the students have an induction programme including attending clinics to see patients and have a series of lectures focused on neuromuscular diseases. Following induction, in the first year at UCL, the students rotate three-monthly through three PI laboratories of their choice. Following this rotation the students select their preferred project for their PhD. During the year the students have regular teaching, lectures and seminars. NCL: In the first year in the four-year non-clinical PhD programme in NCL, the students undertake a Masters by Research (MRes) “Neuromuscular Diseases – Bench to Bedside” which has been developed by the MRC neuromuscular group in NCL utilising the skills and knowledge of the neuromuscular staff and selected pre-eminent colleagues. The course covers the entire breadth of translational science in neuromuscular diseases, from the basic physiology of muscle and neuromuscular transmission, through basic science models, clinical diagnostics, experimental therapeutics to clinical trials and patient benefit.

3 year Clinical PhD programme In the 3 year clinical PhD programme the students undertake either a laboratory or clinical translational (e.g. development of MRI) project together with a significant clinical component (e.g. clinical trial, natural history study). Highlights of the programme include i) the opportunity to attend our annual four day neuromuscular course in ION, ii) all students have to present their work by poster and in some cases by platform presentations at our annual MRC Centre Neuromuscular Translational Research Conference and iii) a yearly students’ retreat that the students organise and run once a year which has proved very popular and educational. In addition, all students are encouraged to attend the multiple scientific educational opportunities in the Centre including monthly MRC seminar series with invited international speakers (also available as web-seminars), regular journal clubs, departmental research meetings and seminars, subject specific workshops and conferences.

Metrics of MRC Centre PhD programme As shown in the table below, we were awarded 16 four-year non clinical, four three-year clinical and 13 one-year clinical pump priming posts in the renewed Centre. These posts were equally funded by the MRC and by the host universities UCL and NCL. By 2015, as planned we had appointed to all posts (Table 1). In the renewed Centre the MRC were keen we appointed clinical fellows for one year (pump priming posts) and that they would then be encouraged to apply for their own MRC training fellowships which are very prestigious and competitive. This became difficult to do as the training system for specialist registrars (SPRs) in neurology in the UK changed in 2013 so that SPRs had to take the full three years off for a predetermined period so the flexibility of the one year posts was not possible. To overcome this we have introduced a system where we appoint clinical PhDs for three years (using a mixed funding model with MRC, host university and other funders) but after 1 year the students have to apply for a MRC training fellowship if they are doing an appropriate project. This model allows recycling of the MRC funding and has been very effective in allowing us to attract and appoint the best PhD students. Four of our appointed clinical PhD students (Maiya Kugathasan, Karen Suetterlin, Helen Devine and Claire Wood) have successfully

1 | P a g e obtained MRC three-year MRC training fellowships following an initial period of MRC Centre funding.

Table 1: MRC Centre Studentships from February 2013 Studentships awarded Appointed To be appointed in Centre Renewal 2013 Non Clinical 4 year Non-clinical PhD (4 yrs.) None posts UCL – 5 (2013) 1/5** UCL – 9 UCL – 2 (2014) NCL – 7 UCL – 3 (2015) NCL – 4 (2013) NCL – 3 (2014) Clinical posts * Appointed Clinical PhD posts** None 12 yrs (4x3year) UCL – 4 (2013) 13 yrs (13x1year) NCL – 4 (2014) UCL – 2 (2015) *years appointed; **alternative funding also used

A further training aim in the MRC Centre renewal was to work with industry to develop joint MRC Centre /industry PhD studentships (CASE studentships). We have successfully done this with GSK and have appointed one CASE studentships in MRI neuromuscular diseases, who started in 2014. We train many other students, post docs and senior fellows in the MRC Centre who are funded by sources other than the MRC but who benefit from the educational and training opportunities in the MRC Centre.

Post PhD mentoring and career progression One of the most important aims of the MRC Centre is to train clinical and non-clinical neuromuscular scientists to develop a critical mass of researchers and clinicians in the UK for the future. We therefore provide ongoing mentoring and career advice for our PhD students and carefully monitor career progression post PhD. Table 2 lists the post-PhD destinations of all the clinical and non-clinical PhD students for the first 5 year grant cycle (2008-2013). To date we have been very successful at helping our trainees secure further positions in neuromuscular diseases. Most of our trainees are either in post-doctoral positions in neuromuscular diseases or are clinical trainees or consultants in neuromuscular diseases. One of our non-clinical PhDs is now doing a medical degree and one is a bioinformatician. A further training aim in the MRC Centre renewal was to work with industry to develop joint MRC Centre / industry PhD studentships (CASE studentships). We have successfully done this with GSK and have appointed a CASE studentship in MRI neuromuscular diseases, who started in 2014.

Table 2: MRC Students next destination PhD Dates next destination MRC Centre Non-Clinical PhD students, UCL Dr Mhoriam Ahmed 2007 – 2011 Neuromuscular Post-Doc, UCL Institute of Neurology Dr Alex Clark 2008 – 2012 iPS Post-Doc, Division of Clinical Neurology, University of Oxford Dr Amy Innes 2007 – 2011 Postgraduate MBBS, St George’s University of London

2 | P a g e Dr Phil McGoldrick 2008 – 2012 Neuromuscular Post-Doc, University of Toronto Dr Alice Neal 2008 – 2012 Post-Doc, Ludwig Cancer Research, University of Oxford MRC Centre Clinical PhD students, UCL Dr Adrian Miller 2008 - 2011 Neurology SpR training, London Dr Jasper Morrow 2009 – 2012 Consultant Neurologist, National Hospital for Neurology & Neurosurgery, & The Lister Hospital, Stevenage MRC Centre Non-Clinical PhD students, Newcastle

Dr Alastair Wood 2008 – 2012 Neuromuscular Post-Doc, Australian Regenerative Medicine Institute, Monash University, Western Australia Dr Sally Spendiff 2007 – 2011 Neuromuscular Post-Doc, McGill University, Montreal, Canada Dr Kieren Lythgow 2007 – 2011 Bioinformatician, Public Health England

Other MRC Centre educational activities The MRC Centre provides an ongoing extensive portfolio of educational and training opportunities. Particular highlights include:  The yearly MRC Centre UK Translational Research Conference. This conference organised jointly by the MRC Centre and the charity Muscular Dystrophy Campaign (MDC) has become the main neuromuscular meeting in the UK with an average of 220 participants yearly. This is a particular highlight for our students and senior fellows and post docs who get to present their research findings yearly. We have made this meeting truly national by alternating the meeting between London, Newcastle and Oxford.  We run a very popular and successful four-day neuromuscular course which is a comprehensive update covering all neuromuscular diseases in UCL yearly and which attracts about 100 attendees annually, many of whom are international.

3 | P a g e Year 1 clinical

Enrico Bugiardini

Start Date: June 2016 PhD Project Title: Clinical, functional and genetic characterization of mitochondrial diseases Supervisors: Professor Mike Hanna, Professor Henry Houlden Funding source: NCG Length of studentship: 3 years

Project Description: Mitochondrial diseases are a group of conditions caused by a dysfunction of the mitochondrial respiratory chain, which is under the dual control of nuclear, and mitochondrial DNA (mtDNA). Mutation of either the nuclear or the mitochondrial genome may cause mitochondrial disease. In recent years several nuclear genes have been associated with mitochondrial function and diseases but there are still several patients without a genetic diagnosis. My main project is focused on studying those patients who still do not have a diagnosis and applying next generation sequencing techniques (genes panel or exome sequencing). The first step will be the identification of new genes causing mitochondrial disease or new clinical manifestations of known genes. This will have a direct clinical benefit for the patient in terms of management and genetic counselling. The second step will be studying the mechanism underlying the mitochondrial damage caused by those nuclear genes. A better understanding of mitochondrial function/dysfunction holds the clue for future therapy focused on restoring mitochondrial efficiency. As mitochondrial disease often presents with muscle symptoms I will extend the analysis to patients affected by muscle diseases. Finally as well as the genetic studies I am involved in a clinical study through the MRC Centre Mitochondrial Disease Patient Cohort. This represents a national registry containing all the clinical, genetic and demographic information of patients affected by mitochondrial disease in UK. I am directly involved in the collection and analysis of data of patients belonging to the London site. One specific study that is ongoing is evaluating the cause of death in patients with mitochondrial diseases. A better understanding of this may have direct implication on clinical management of people affected by mitochondrial diseases.

Significant Publications: Long-term Safety and Efficacy of Mexiletine for Patients with Skeletal Muscle Channelopathies. JAMA Neurol. 2015 Dec 1;72(12):1531-3. PMID: 26658970 Suetterlin KJ, Bugiardini E, Kaski JP, Morrow JM, Matthews E, Hanna MG, Fialho

4 | P a g e Joana Domingos

Start Date: September 2015 PhD Project Title: Biomarkers of Duchenne muscular dystrophy disease progression Supervisors: Professor Francesco Muntoni, Professor Jennifer Morgan Funding source: GOSH BRC (Host matched funding) Length of studentship: 3 years

Project Description: Duchenne Muscular Dystrophy (DMD) is a life-limiting X-linked inherited muscle disorder that occurs as a result of loss of function mutations in the dystrophin gene. There is a well-known clinical variability that not only affects counselling of individual patients and standards of care, but also clinical trial design and assessment of clinical efficacy in small cohorts of patients recruited into experimental therapeutic trials. This is compounded by the relative rarity of DMD, and the complexity of running large clinical trials. In this context, the identification and validation of new DMD biomarkers is becoming increasingly important. Recently, candidate genetic disease-modifier Single Nucleotide Polymorphisms (SNPs) such as SPP1 and LTBP4 have been described in different cohorts of DMD patients. Other SNPs have been recently identified by our group as part of an EU funded biomarker discovery project, Bio-NMD (www.bio-nmd.eu) but have not been validated yet in larger patient populations. In broad terms, the aim of this project is to contribute to a better understanding and characterization of the biomarkers that might influence disease progression in DMD. In particular, we aim to validate the previously described genetic biomarkers and potentially identify new ones in relation to motor and cardiac function. Another step forward would be to carry out functional studies on the SNPs of interest identified and validated in the DMD cohort, so that we could contribute to further elucidate DMD pathophysiology.

Kate Maresh

Start Date: April 2016 PhD Project Title: Deep phenotyping of the central nervous system in dystrophinopathies Supervisor: Professor Francesco Muntoni Funding source: MRC Centre Grant Length of studentship: 3 years

Project Description:

5 | P a g e Duchenne muscular dystrophy (DMD) and its milder allelic variant, Becker muscular dystrophy (BMD), are X-linked neuromuscular conditions caused by mutations in the DMD gene. In DMD, a lack of dystrophin leads to progressive muscle inflammation and damage, and many patients also exhibit symptoms related to central nervous system (CNS) dysfunction, including non-progressive learning difficulties, attention deficit disorder, anxiety and autism. The function of dystrophin in the brain is not known. The dystrophin gene contains 7 promoter regions, each coding for different tissue-specific dystrophin isoforms. Full length dystrophin (Dp427) is expressed in muscle, brain and cerebellar Purkinje cells, and a number of shorter isoforms are also specifically expressed in the central nervous system (CNS). Mutations which lead to loss of the shortest isoforms correlate with increased cognitive impairment in DMD, but the genotype-phenotype association is less clear in BMD and in other aspects of CNS function. A mouse model of DMD (mdx mouse), which lacks the full-length Dp427 isoform of dystrophin, exhibits enhanced defensive behaviour and freezing response. Dp427 localises to the postsynaptic region of GABA-ergic neurons in the mouse, and in the mdx mouse there is impaired GABA-ergic signaling in the amygdala, which is involved in the fear response. These behaviours in the mouse have been improved in mdx mice treated with exon-skipping antisense oligonucleotide treatments, suggesting that at least some of the CNS effects of lack of dystrophin may be reversible. I will conduct deep-phenotyping of the CNS phenotype in DMD and the milder allelic Becker muscular dystrophy (BMD) variant patients with the following aims: - to develop a standardised testing protocol of neuropsychology tests to be used in DMD & BMD - to perform structural and functional brain MRI and electroretinography (ERG) studies in a subset of patients - to correlate the findings of these studies with the location of the dystrophin mutations in a phenotype-genotype analysis

Year 2 non-clinical

Benjamin O’Callaghan

Start Date: September 2015 PhD Project Title: The impact of mitochondrial impairment on histone acetylation profiles Supervisors: Professor Henry Houlden, Professor Jenny Morgan Funding source: UCL matched funding (MRC Centre Grant) Length of studentship: 4 years

Project Description: During my first 3 month rotation I looked at the effect mutations in mitochondrial DNA have on the differentiation of induced pluripotent stem cells (IPSCs) into myotubes. Mitochondrial diseases are a heterogeneous group of disorders caused by genetic dysfunction of mitochondrial oxidative phosphorylation. IPSCs derived from mitochondrial disease patients and appropriate differentiation towards affected cell types (e.g. muscle and neurons) represents an excellent model to explore disease mechanisms for novel targeted therapeutic intervention. Mutations in a potassium channel gene KCNJ18 have recently been associated with TPP however this has been disputed due to the high prevalence in healthy control individuals. During my second rotation I looked into the genetics of TPP with particular focus on KCNJ18 and the closely related KCNJ12 genes.

6 | P a g e Environmental stressors are thought to play an important role in the initiation and progression of amyotrophic lateral sclerosis (ALS). Recent evidence has revealed that stress granules might represent a focal point linking external stress with genetic susceptibility. During my final 3 month rotation I have been optimising an in vitro model of motor neuron injury to investigate the cellular localisation of RNA-binding proteins associated with ALS.

Benjamin Clarke

Start Date: September 2015 PhD Project Title: The role of the heat shock response in mitochondrial dysfunction in motor neuron disease Funding source: UCL matched funding (MRC Centre Grant) Length of studentship: 4 years Project Supervisors: Dr Bernadett Kalmar, Prof Linda Greensmith

Project description: Mitochondrial dysfunction has been implicated in contributing to the death of motor neurons in Amyotrophic lateral sclerosis (ALS). Heat shock proteins are a family of pro-survival chaperones known to possess anti-aggregation and anti-apoptotic capabilities which aid motor neuron survival. Several heat shock proteins localise to mitochondria although their roles in motor neurons are not fully understood. My PhD project will investigate the importance of heat shock proteins to mitochondrial dysfunction in models of ALS and attempt to ameliorate mitochondrial dysfunction through the pharmacological upregulation of heat shock proteins.

Verna Sarajarvi

Start Date: September 2015 PhD Project Title: Investigating cellular pathomechanisms of Charcot-Marie-Tooth disease Funding source: UCL matched funding (MRC Centre Grant) Length of studentship: 4 years Project Supervisors: Dr Bernadett Kalmar, Prof Mary Reilly

Project description: I carried out my first rotation project at the UCL Institute of Child Health in Professor Francesco Muntoni's group. The project was aimed at developing a gene therapy approach for Hereditary Sensory Neuropathy type 1. During my second rotation project I was investigating mitochondrial diseases in Professor Michael Duchen's laboratory. I completed my third and final rotation project in Professor Linda Greensmith's group studying the pathomechanisms of axonal Charcot-Marie-Tooth disease.

7 | P a g e Hadil Alrohaif

Start date: September 2015 MD Project title: Next generation sequencing in diagnostics and disease gene discovery: A systematic assessment of integrated genomic platforms in rare neuro-genetic disease Supervisors: Professor Hanns Lochmüller, Dr Ana Topf, Rachel Thompson Funding source: Kuwaiti Government Length of studentship: 3 years

Project description: This project will take a systematic bioinformatics approach in evaluating three integrated genomic platforms used in prioritising genes and variants from next generation sequencing (NGS) projects in neurogenetic disease. Up to 1,000 WES/WGS datasets will be available for analysis, on at least two platforms each. These platforms, namely: RD-Connect (CNAG, Barcelona, academic), Seqr(Broad Institute, Boston, academic) and Clinical Sequence Analyser (WuXi NextCODE, commercial), will be initially assessed for sensitivity, specificity and diagnostic yield of solved and unsolved cases. An in- depth analysis of VCF filtering algorithms, variant annotation, user filtering options, and integration with relevant genomic, phenotypic and bioinformatics applications will be carried out and compared across platforms. Findings will be used in an attempt to further develop diagnostics and disease gene discovery in rare neurological disease. My hypothesis is that through standardization of the bioinformatics pipeline, integration of machine-readable deep phenotypic information, and matchmaking the number of correctly solved cases can be increased. In addition, the comparison between platforms will reveal strengths and weaknesses which may aid developers to design and implement improvements.

Year 2 Clinical

Olivia Poole

Start Date: August 2015 PhD Project Title: Mitochondrial disease: clinical studies and molecular mechanisms Supervisors: Professor Mike Hanna, Dr Rob Pitceathly Funding source: Lily Foundation Length of studentship: 3 years

Project Description:

8 | P a g e Mitochondrial diseases encompass a phenotypically, biochemically and genetically heterogeneous group of disorders caused by impaired oxidative phosphorylation. Their complexity is, in part, related to the dual genomic expression of mitochondrial proteins which are encoded by both nuclear and mitochondrial DNA. The main aim of my project is to identify novel nuclear genes underpinning mitochondrial dysfunction, using next generation sequencing technology, and to characterise the pathological effects of these mutations using functional studies. My research will also evaluate the clinical impact of mitochondrial disease on organ function

Significant Publications: Poole, O. V., Hanna, M. G., & Pitceathly, R. D. (2015). Mitochondrial Disorders: Disease Mechanisms and Therapeutic Approaches. Discovery medicine, 20(111), 325- 331. PMID:26645904

Helen Devine

Start Date: September 2013 (maternity leave April 2014 to Apr 2015), (maternity leave Aug 2016 to Aug 2017) PhD Project Title: The Pathogenesis of Spinal Bulbar Muscular Atrophy Supervisors: Professor Michael Hanna, Professor Linda Greensmith, Dr Rickie Patani Funding source: Kennedy’s fund followed by MRC Clinical Research Training Fellowship Length of studentship: 3 years

Project Description: Spinal and Bulbar Muscular Atrophy (SBMA) is a neurodegenerative disorder caused by a polyglutamine repeat in the Androgen Receptor gene. It leads to a motor neuron (MN) disease in males who present with weakness in bulbar and limb muscles in their fourth to sixth decade. Previous research in SBMA has been performed in cell and rodent models which do not truly recapitulate the human disease; there is, therefore, a need for a human model. This is possible using induced pluripotent stem cells (iPSCs). Although SBMA is a rare disease, it is particularly interesting as it has parallels to both other MN diseases and other polyglutamine disorders such as Huntington’s Disease which also have a neurodegenerative phenotype. The goals of my project are to: 1. Develop a human model of SBMA by differentiating iPSCs from SBMA patients into bulbar and spinal MN and astrocytes co-cultured with iPSC spinal MN 2. Investigate pathways of neurodegeneration implicated in MN disease: axonal transport deficits, protein mishandling and aggregation, endoplasmic reticulum stress, mitochondrial dysfunction and the role of disturbed astroglial-neuronal interaction 3. Determine if MN deficits can be ameliorated. Compounds which target protein mishandling and axonal transport are currently available for assessment

Significant Publications: Whittaker RG, Devine HE, Gormon GS, Schaefer AM, Horvath R, Ng Y, Nesbitt V, Lax NZ, McFarland R, Cunningham MO, Taylor RW, Turnbull DM Epilepsy in adults with mitochondrial disease: A cohort study (2015) Annals of Neurology 78(6) 949-57 PMID: 26381753 Devine H, Parton M (2015) Tips from the shop floor: Seizure: Acute management and investigation British Journal of Hospital Medicine Devine H, Rohrer J (2015) Next Generation Neurology: The ABNT mentoring program ACNR 15(3):17

9 | P a g e Tallantyre E, Devine H (2014) The Shape of Training: what is it and how does it affect neurology? ACNR 14 (4): 22-24

Next destination: My aim is to apply for further funding after completion of my PhD in order to continue my research whilst completing my neurology training.

Grace McMacken

Start date: September 2015 PhD Project Title: Adrenergic Signalling and Congenital Myasthenic Syndromes Supervisors: Professor Hanns Lochmϋller, Dr Andreas Roos Funding Source: Association of British Neurologists/Guarantors of Brain Clinical Research Training Fellowship Length of studentship: 3 years

Project Description: Therapies acting on the sympathetic nervous system have been shown to have beneficial effects in several neurological diseases. More recently, sympathomimetics have been shown to be beneficial with certain types of congenital myasthenic syndromes (CMS). However, the mechanism by which the sympathetic nervous system exerts these effects on neuromuscular transmission is not understood. The aim of this project is to explore the mode of action of sympathomimetics at the neuromuscular junction (NMJ) development and structure, and to characterise the principle route by which adrenergic modulation exerts a physiological effect. The effect of the adrenergic agonists salbutamol and ephedrine will be studied in vivo using CMS zebrafish and mouse models which closely resemble the human disease, allowing the analysis of pre and post-synaptic effects of these drugs throughout NMJ maturation. An understanding of the effect of sympathomimetics at the NMJ will be instrumental in order to target treatment to the most appropriate patient groups, and will facilitate the development of more targeted therapies, which benefit skeletal muscle function while minimizing systemic .

Boglarka Bansagi

Start date: February 2014 PhD Project Title: Clinical and genetic characterisation of hereditary motor neuropathies Supervisors: Professor Rita Horvath Funding Source: MRC studentship Length of studentship: 3 years

10 | P a g e Project Description: The aim of the clinical project is to enhance the national cohort of Charcot Marie Tooth disease with patients diagnosed in North England. This cohort will enable us to proceed with natural history and genetic studies in this gross patient group both nationwide and locally. The project is primarily focused on the subgroup of distal hereditary motor neuropathies (dHMN). We plan to identify new genes and establish further subclassification of dHMN on a clinico-genetic basis. This will provide us with new insights of the pathomechanisms of the disease and will hopefully allow us to identify biomarkers in this subgroup.

Significant publications: Balreira A, Boczonadi V, Barca E, Pyle A, Bansagi B, Appleton M, Graham C, Hargreaves IP, Rasic VM, Lochmüller H, Griffin H, Taylor RW, Naini A, Chinnery PF, Hirano M, Quinzii CM, Horvath R. ANO10 mutations cause ataxia and coenzyme Q deficiency. J Neurol 2014;261(11):2192-2198. Herrmann DN, Horvath R, Sowden JE, Gonzalez M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi₁₀ V, Lochmüller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S. Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. Am J Hum Genet 2014;95(3):332-339. Boczonadi V, Bansagi B, Horvath R. Reversible infantile mitochondrial diseases. J Inherit Metab Dis 2015;38(3):427-435. Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzińska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Am J Hum Genet 2014;95(5):590-601. Evangelista T, Bansagi B, Pyle A, Griffin H, Douroudis K, Polvikoski T, Antoniadi T, Bushby K, Straub V, Chinnery PF, Lochmüller H, Horvath R. Phenotypic variability of TRPV4 related neuropathies. Neuromuscul Disord 2015;25(6):516-521. Bansagi B, Antoniadi T, Burton-Jones S, Murphy SM, McHugh J, Alexander M, Wells R, Davies J, Hilton-Jones D, Lochmüller H, Chinnery P, Horvath R. Genotype/phenotype correlations in AARS- related neuropathy in a cohort of patients from the United Kingdom and Ireland. J Neurol 2015; 262(8):1899-1908. Bansagi B, Griffin H, Ramesh V, Duff J, Pyle A, Chinnery PF, Horvath R. The p.Ser107Leu in BICD2 is a mutation 'hot spot' causing distal spinal muscular atrophy. Brain 2015;138(Pt 11):e391. Whittaker RG, Herrmann DN, Bansagi B, Hasan BA, Lofra RM, Logigian EL, Sowden JE, Almodovar JL, Littleton JT, Zuchner S, Horvath R, Lochmüller H. Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome. Neurology 2015;85(22):1964-1971.

Katarzyna Swist-Szulik

Start date: October 2013 (research associate part-time), May 2014 (MRC studentship) PhD Project Title: Does mitochondrial dysfunction influence NLRP3 inflammasome activation and other cell signalling pathways? Supervisors: Professor Sir Doug Turnbull, Dr Robert McFarland, Professor Rob Taylor, Professor Derek Mann and Dr Lee Borthwick (Fibrosis and Inflammation Group)

11 | P a g e Funding Source: MRC studentship Length of studentship: 3 years

Project Description: The project aims to improve our understanding of the role of mitochondrial dysfunction in inflammatory responses in both myeloid and non-myeloid cells and investigate the hypothesis that cells with mitochondrial injury can influence signalling transduction pathways and inter-cellular interactions. We have identified that fibroblasts and myoblasts with induced mitochondrial dysfunction by Rotenone (complex I inhibitor) and recombinant interleukin IL-1β produce extremely high levels of interleukin IL-6 in dose dependent manner. In experiments using a migration assay we demonstrated that fibroblasts and myoblasts with induced mitochondrial injury attract far more immune cells, such as THP1 immortalised monocytes, than healthy cells. Pro- inflammatory interleukin IL-6 appears to play an important role in the migration of these immune cells. These findings may be relevant to disease processes presenting with both mitochondrial and inflammatory components.

Year 3 non-clinical

Ione Meyer

Start Date: Sept 2014 PhD Project Title: Investigating reciprocal interactions at the neuromuscular junction in models of neurodegenerative disease Supervisors: Professor Giampietro Schiavo, Professor Elizabeth Fisher Funding source: MRC Centre Grant Length of studentship: 4 years

Project Description: Motor neuron death is a pathological hallmark of a number of neurodegenerative diseases including ALS and SMA. Growing evidence indicates that this degeneration begins at distal regions, with changes at the neuromuscular junction (NMJ) preceding motor neuron cell death and the onset of clinical symptoms. Interestingly, there appears to be a selective vulnerability of specific motor neuron classes (fast fatigable) and their innervated muscle fibre types. Taken together, these results suggest the existence of factors at the NMJ that influence vulnerability, or resistance, to degeneration. It is therefore important to increase our understanding of the reciprocal interactions between motor neurons and the motor endplate in health and disease. Our lab have recently identified a novel retrograde signalling pathway that involves the mobilisation and uptake by motor neurons of a group of extracellular proteins called nidogens, also known as entactins, from the basement membrane at the neuromuscular synapse. The binding affinity of nidogens for several components of the basement membrane indicates that these proteins are involved in stabilisation of the extracellular matrix. However, our results suggest an additional intracellular signalling role for nidogens. We aim to further investigate the physiological function of nidogens at the NMJ, by examining nidogen isoform expression in cultured motor neurons and ex vivo muscles using fluorescence microscopy. Co-localisation studies will also be performed to explore protein interactions, which may shed light on the role of nidogen signalling. This work will lead to a greater understanding of the processes regulating NMJ integrity, and thereby reveal potential targets for therapeutic intervention to combat NMJ pathology in devastating neurodegenerative diseases

12 | P a g e Stephanie Carr

Start date: September 2014 PhD project title: Cardiac targeted therapy studies in Duchenne Muscular Dystrophy Funding source: Barbour Foundation Length of studentship: 4 years (1 year MRes + 3 years PhD) Supervisor: Prof Hanns Lochmüller

Project description: In patients with Duchenne Muscular Dystrophy (DMD), both skeletal and cardiac muscle lack dystrophin protein and degenerate progressively, leading to loss of independence and premature death. While the primary genetic defect is identical for the heart and skeletal muscle, the symptoms and severity are often dissociated pointing towards different secondary, organ-specific events and pathways. Moreover, several innovative therapies that are currently in clinical development such as exon skipping via antisense oligonucleotides seem to be more efficient in the dystrophin-deficient muscle than the heart. To understand the different pathways acting in the dystrophic heart and to develop therapies targeting the heart in DMD, we have generated a specific, new assay. For our assay, we culture primary heart cells from dystrophin-deficient mdx mice (cardiomyocytes) and subject them to stress via serum starvation. Unlike healthy dystrophin-positive cardiomyocytes, mdx cells show a specific hypertrophic response that can be partially reversed by cardio-protective drugs. Therefore, this assay can be utilized to assess therapeutic interventions (drugs or genetic) for whether they show benefit for dystrophic heart cells. Moreover, data obtained through RNA sequencing of different time points in the hypertrophic response of the dystrophic cells in comparison with the normal cells, revealed a number of pathways that are specific for dystrophin- deficiency and some that are specific for the heart. This project will continue to use this assay to test therapies for potential efficacy in the heart as well as using it as a tool to investigate specific genes and pathways involved in the hypertrophic response.

Persefoni Ioannou

Start Date: September 2014 PhD Project Title: NHE1 inhibition as a potential therapy for Duchenne Muscular Dystrophy (DMD) Supervisor: Professor Volker Straub Funding source: MRC, Barbour Foundation Length of studentship: 3 years

Project Description:

13 | P a g e The absence of dystrophin in Duchenne Muscular Dystrophy (DMD) muscle cells results in increased membrane permeability and subsequent intracellular calcium overload. The dysregulation of calcium homeostasis that characterizes the DMD models is exacerbated by the increased activity of the Sodium/Hydrogen Exchanger 1 (NHE1). NHE1 over-activity leads to an increased influx of sodium, which in turn switches the Sodium/Calcium Exchanger (NCX) into reverse mode, resulting in an increased calcium influx. Selective NHE1 inhibitors can be used to reduce the sodium influx and thereby, revert the NCX to normal mode with a subsequent decrease in the cellular calcium load. This observation has led to the hypothesis that the use of specific NHE1 inhibitors could improve the calcium homeostasis and alleviate pathology in DMD muscle. The current study seeks to demonstrate the efficacy of a specific NHE1 inhibitor that has shown a good safety and potency profile in several pre-clinical studies. The study employs a series of methods including manganese-enhanced molecular resonance imaging (MEMRI), histological analysis, and functional grip strength test, in order to assess the efficacy of the drug after in vivo treatment of mdx mice, a DMD model. The study will be supplemented with in vitro pH, sodium and calcium assays that will be used to verify the drug action. The proposed studies with a first prototype NHE1 inhibitor are an important step towards potential clinical trials for dystrophinopathies with this class of compounds.

Aura Cecilia Jimenez Moreno

Start Date: September 2014 PhD Project Title: Assessing habitual physical activity in Myotonic Dystrophy type 1 and its impact on disease severity Supervisors: Professor Hanns Lochmüller, Dr. Grainne Gorman and Dr. Sarah Charman Funding source: MRC, Barbour Foundation and Conacyt Mexico. Length of studentship: 3 years

Project Description: Myotonic Dystrophy type 1 (DM1) is the most common muscular dystrophy in adults and due to a mutation on the DMPK gene it manifests with an heterogeneous phenotype. However, one of the symptoms patient report to impact more on their daily life functionality has been fatigue which with the underlying progressive muscle weakness leads to a sedentary behaviour associated with poor health outcomes and distinctive physiological consequences in healthy adults. In different debilitating disorders, the association between habitual physical activity (HPA) levels and clinical phenotype has been shown and has also been suggested for DM1. However a valid objective outcome measure is required to quantify this and demonstrate if there is any association between these two variables, HPA and disease burden. The aim of my PhD is to validate the use of an accelerometer to measure HPA in DM1 and analyze its association with disease burden at baseline and prospectively over time. This study is part of an ongoing international trial oriented to increase physical activity in DM1 with the aim to improve patients quality of life and reduced fatigue severity and variables to consider include, functional outcomes, patient reported outcomes, blood biomarkers and cardiac function analyzed by MRI.

Relevant Publications:

14 | P a g e van Engelen B and the OPTIMISTIC Consortium. Cognitive behaviour therapy plus aerobic exercise training to increase activity in patients with myotonic dystrophy type 1 (DM1) compared to usual care (OPTIMISTIC): study protocol for randomised controlled trial. Trials. 2015;16(1):224.

Prasanth Sivakumar

Start Date: September 2014 About to enter year 3 of 4 PhD Project Title: Investigating dysfunctional RNA processing in TDP-43 mouse mutants Supervisors: Professor Elizabeth Fisher, Pietro Fratta Funding source: MRC Centre Grant Length of studentship: 4 years

Project Description: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive disorder characterised by degeneration of both upper and lower motor neurons, resulting in muscular atrophy. Recently, RNA processing has been implicated in ALS pathology, notably the depletion of RNA-binding protein TDP-43 from the nucleus and its subsequent cytoplasmic aggregation in the vast majority of ALS cases. My aim is to investigate the genotypic consequences of aberrant TDP-43 activity on RNA processing. Changes to the motor neuron transcriptome will be analysed using newly developed techniques enabling cell-specific gene expression analysis, and through these methods I hope to further our understanding of the role TDP-43 dysfunction plays in ALS.

Year 3 clinical

Maiya Kugathasan

Start Date: April 2013 PhD Project Title: Hereditary Sensory Neuropathy Type 1 secondary to SPTLC1/2 mutations: Pathogenesis and treatment Supervisors: Professor Mary M Reilly & Professor Linda Greensmith Funding source: NIH Rare Disease Inherited Neuropathy Fellowship (1 year), MRC Centre Grant, followed by MRC clinical training fellowship (3 years) Length of studentship: 4 years

Project Description:

15 | P a g e Hereditary Sensory Neuropathy Type 1 (HSN1) secondary to SPTLC1/2 mutations is a rare, slowly progressive neuropathy leading to profound sensory loss with variable but often severe motor involvement. At the National Hospital for Neurology and Neurosurgery, we have the largest cohort of patients with this condition in the world. We have a unique population within the United Kingdom where all the SPTCL1 patients have a common mutation (C133W). Recent studies have shown that mutations in these two genes, which encode an enzyme, lead to the build of atypical metabolites called deoxysphingolipids which are postulated to be neurotoxic. My project has three aims. Firstly, to investigate the role of deoxysphingolipids in HSN1 using primary motor neuron and DRG culture models. Secondly to investigate the therapeutic potential of L-serine supplementation using induced pluripotent stem cell derived sensory neurons from patients’ fibroblasts (Professor Bennett’s lab in Oxford). Thirdly, to identify outcome measures for a therapeutic trial in HSN1 patients by undertaking a one year natural history study.

Karen Suetterlin

Start Date: September 2013 (maternity leave January 2015 to October 2015) (maternity leave 12 May 2016 to est. Jan 2017) PhD Project Title: A Molecular Pathophysiological Study of the Skeletal Muscle Channelopathies Funding source: EU FP7 Research and innovation followed by MRC Research fellowship Supervisor: Professor Michael Hanna, Dr Emma Matthews, Dr Roope Männikkö Length of studentship: 4 years

Project Description: Myotonia congenita is caused by mutations in the chloride channel gene. Mutations are found throughout the entire channel, can be dominant or recessive and in some cases both patterns of inheritance have been reported for the same mutation. This makes genetic counselling and determining the likely clinical significance of new variants very difficult. To try to address this I used our large data set to investigate how functional characterisation and variant location might help estimate the risk of a variant being disease causing and/or associated with a dominant mode of inheritance. I functionally characterised 5 novel chloride channel variants and built a homology model of a chloride channel in its functional form as a dimer. I mapped over 80 variants that have been functionally characterised by our centre onto this model and categorised over 200 patients with these variants according to their reported inheritance pattern of clinical symptoms. Variants clearly clustered on the model according to their functional effect and associated inheritance pattern. Combining a variant’s location and functional effect with the associated inheritance pattern has enabled us to provide a framework to assess the risk of an associated dominant mode of inheritance and highlight those variants most likely to be benign polymorphisms. In the second part of my PhD I will investigate progressive age related weakness in periodic paralysis and normal ageing. My hypothesis is that age related changes may reduce the muscle’s homeostatic reserve to deal with the chronic consequences of single ion channel dysfunction. I will investigate how excitation-contraction coupling and the skeletal muscle ‘channelome’ change with age in periodic paralysis and normal muscle. I will also look at the effect of prolonged depolarisation, as occurs during an attack of paralysis, on the muscle as a whole and how age

16 | P a g e affects this. My aim is to improve our understanding of the mechanisms involved in the development of progressive age related weakness and how acute attacks of paralysis may contribute to permanent weakness in periodic paralysis.

Significant Publications: Zaharieva IT, Thor MG, Oates EC, van Karnebeek C, Hendson G, Blom E, et al. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy. Brain : a journal of neurology. 2015. Epub 2015/12/25. Suetterlin KJ, Bugiardini E, Kaski JP, Morrow JM, Matthews E, Hanna MG, et al. Long-term Safety and Efficacy of Mexiletine for Patients With Skeletal Muscle Channelopathies. JAMA neurology. 2015;72(12):1531-3. Epub 2015/12/15. Suetterlin K, Turner C. Diagnosis and management of headache. Br J Hosp Med (Lond). 2014;75(12):C178-82. Epub 2014/12/10. Suetterlin K, Mannikko R, Hanna MG. Muscle channelopathies: recent advances in genetics, pathophysiology and therapy. Current opinion in neurology. 2014;27(5):583-90. Epub 2014/09/05. Suetterlin K & Hanna, M.G. Muscle Channelopathies. Chapter 116. International Neurology: A Clinical Approach. 2nd Edition. Wiley Blackwell. In press, to be published April 2016.

Elizabeth Harris

Start date: October 2013 PhD Project Title: Next generation sequencing and deep phenotyping in limb girdle muscular dystrophies Supervisors: Professor Kate Bushby, Professor Volker Straub, Dr Ana Topf Funding Source: Muscular Dystrophy UK Clinical Training and Research Fellowship Length of studentship: 3 years (plus 8 month extension for maternity leave)

Project Description: Limb girdle muscular dystrophies (LGMD) are a clinically and genetically heterogeneous group of rare disorders that cause progressive weakness and wasting of proximal muscles. Although the number of genes known to cause LGMD has increased in recent years there remains a small proportion of patients in who a genetic diagnosis is not achieved. This project applies whole exome sequencing to identify the pathogenic genetic variants underlying LGMD, which may be in known or novel disease genes. Once diagnosed, obtaining a comprehensive understanding of the phenotype and progression of these rare diseases is essential for the design of successful clinical trials. I clinically assess patients with genetically confirmed LGMD type 2B, due to mutations in the dysferlin gene as part of an international multicentre natural history study, and analysis of data from this study is also performed as part of this project.

Significant Publications: 1. Harris E, Bladen CL, Mayhew A, James M, Bettinson K, Moore U, et al. The Clinical Outcome Study for dysferlinopathy: An international multicenter study. Neurology Genetics. 2016 Aug;2(4):e89. PubMed PMID: 27602406. Epub 2016/09/08. eng. 2. Steele HE, Harris E, Barresi R, Marsh J, Beattie A, Bourke JP, et al. Cardiac involvement in hereditary myopathy with early respiratory failure: A cohort study. Neurology. 2016 Sep 6;87(10):1031-5. PubMed PMID: 27511179. Epub 2016/08/12. eng.

17 | P a g e 3. Figueroa-Bonaparte S, Hudson J, Barresi R, Polvikoski T, Williams T, Topf A, et al. Mutational spectrum and phenotypic variability of VCP-related neurological disease in the UK. Journal of neurology, neurosurgery, and psychiatry. 2016 Jun;87(6):680-1. PubMed PMID: 26105173. Pubmed Central PMCID: PMC4893144. Epub 2015/06/25. eng. 4. Nasim Vasli*, Elizabeth Harris*, Jason Karamchandani, Eric Bareke7, Jacek Majewski, Norma B. Romero et al. Recessive mutations in the kinase ZAK cause a congenital myopathy with fiber type disproportion. Accepted for publication in Brain, August 2016. * denotes that these authors contributed equally to this work

Alexander Murphy

Start date: August 2014 PhD Project Title: Magnetic resonance imaging of cardiomyopathy secondary to neuromuscular disease and the dystrophinopathies Supervisors: Professor Straub, Dr Hollingsworth, Dr Bourke. Funding source: Bioimage NMD Length of studentship: 3 years

Project description: Neuromuscular outcome measurements should be reliable, sensitive, clinically relevant and linked to the underlying disease process. This PhD project explores the use of MRI as a neuromuscular outcome measure for some types of muscular dystrophy. Although MRI has been used in several ways to measure neuromuscular disease progression, so far it has not been able to quantify fibrosis within skeletal or cardiac muscle. LGMD2I, one of the most common types of LGMD has previously only been described with MRI in a one year follow up study. My work will examine: 1. Whether a novel gadolinium-based contrast agent can accurately quantify fibrosis within skeletal and cardiac muscle. 2. Whether the same contrast agent is sensitive enough to detect changes in fibrosis due to administration of an anti-fibrotic. 3. Whether MRI can be used to detect disease progression in a cohort of patients with LGMD2I over a five year period and then compare this to existing neuromuscular outcome measures. 4. Whether MRI can be used to detect disease progression within the heart using novel methods of measurement. 5. Whether MRI can be improved as an outcome measure by reducing acquisition times. Relevant publications: Murphy AP, Straub V. The Classification, Natural History and Treatment of the Limb Girdle Muscular Dystrophies. Journal of Neuromuscular Diseases, vol. 2, no. s2, pp. S7-S19, 2015

18 | P a g e Yi Ng

Start date: August 2013 PhD Project Title: Understanding the phenotype-genotype correlation in mitochondrial disease Supervisors: Dr Robert McFarland, Professor Sir Doug Turnbull and Professor Rob Taylor Funding Source: MRC Clinical PhD Studentship Length of studentship: 3 years

Project Description: The MRC Mitochondrial Disease Patient Cohort is a national collaborative project that has been launched since 2009. The main aims are to better understand the phenotypic and genotypic heterogeneity of mitochondrial disease and facilitate patient recruitment for basic science research and clinical study. To date, more than 1150 patients are registered in the cohort database and more than 55% of patients are recruited in Newcastle. My PhD study is integrated with this cohort project. The cores are to clinically deep phenotype patients and family pedigrees affected by mitochondrial disease caused by different genetic mutations, analyse their disease burdens using Newcastle Mitochondrial Disease Adult Scale (NMDAS) and other investigations (such as brain, cardiac and gastrointestinal imaging) in order to better elucidate the natural history. Ultimately, these findings hopefully could be translated back to clinical practice by providing more accurate data on genetic counselling, prognostication and streamline the guidance on disease management.

Significant publications: Ng YS, Feeney C, Schaefer AM, Holmes CE, Hynd P, Alston CL, Grady JP, Roberts M, et al. Pseudo-obstruction, stroke and mitochondrial dysfunction: A lethal combination. Annals of neurology. Jul 25 2016. Ng YS, Grady JP, Lax NZ, Bourke JP, Alston CL, Hardy SA, Falkous G, Schaefer AG, Radunovic A, Mohiddin SA, Ralph M, Alhakim A, Taylor RW, McFarland R, Turnbull DM, Gorman GS (2015) Sudden adult death syndrome in m.3243A>G-related mitochondrial disease: an unrecognized clinical entity in young, asymptomatic adults. European heart journal Ng YS, Alston CL, Diodato D, Morris AA, Ulrick N, Kmoch S, Houstek J, Martinelli D, et al. The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease. Journal of medical genetics. Jul 13 2016. Ng Y, Turnbull D (2015) Mitochondrial disease: genetics and management. Journal of neurology:1- 13 (60%) Anagnostou ME, NG YS, Taylor RW, McFarland R. Epilepsy due to mutations in the mitochondrial polymerase gamma (POLG) gene: a clinical and molecular genetic review (Joint first author, accepted in Epilepsia on 26th July 2016)

19 | P a g e Renata Scalco

Start Date: Sept 2013 PhD Project Title: Translational research studies in exercise related muscle disorders Supervisors: Professor Michael G Hanna, Dr Ros Quinlivan, Dr Doreen Fialho Funding source: CAPES Foundation, Ministry of Education of Brazil Length of studentship: 3 years

Project Description: Translational research (TR) is the research that transfers knowledge from basic science to clinical setting thus making findings from basic science useful for practical applications and aiming to improve patient care within a relatively short period. This PhD research will translate knowledge from animal models of Hypokalaemic Periodic Paralysis (HypoPP) and McArdle Disease to identify new treatments for both conditions. It includes two phase II clinical trials: an open label uncontrolled pilot study to evaluate safety and efficacy of sodium valproate in McArdle Disease; and an RCT of Bumetanide in HypoPP. Outcome measurements including neurophysiology, exercise functional tests and muscle biopsy analysis will be assessed for the benefit of future studies. A further project aims to evaluate a group of patients presenting with exercise induced rhabdomyolysis. This involves clinical and histopathological studies as well as genetic testing using next generation sequencing. The identification of new well-characterised patient cohorts will facilitate future translational studies.

Significant Publications: Scalco, RS, Snoeck M, Quinlivan R, et al. Exertional rhabdomyolysis: Physiological response or manifestation of an underlying myopathy? BMJ Open Sport & Exercise Medicine. In press Scalco, RS, Gardiner AR, Pitceathly RD, et al. CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: Expanding the phenotypic spectrum of caveolinopathies. Neuromuscul Disord. 2016 Aug;26(8):504-510. Scalco RS, Voermans NC, Piercy RJ, Jungbluth H, Quinlivan R. Dantrolene as a possible prophylactic treatment for RYR1-related rhabdomyolysis. Eur J Neurol. 2016 Aug;23(8):e56-7. doi: 10.1111/ene.13051. Scalco RS, Gardiner AR, Pitceathly RD, et al. Rhabdomyolysis: a genetic perspective. Orphanet J Rare Dis. 2015 May 2;10:51. doi: 10.1186/s13023-015-0264-3 PMID: 25929793 Scalco RS, Brady S, Becker J, et al. LETTER TO THE EDITOR Atypical Granulomatous Myositis and Pulmonary Sarcoidosis. Open Rheumatol J. 2015 Jul 10;9:57-9. doi: 10.2174/1874312901409010057. PMID: 26312107 Quinlivan R, Lucia A, Scalco RS, et al. Report on the EUROMAC McArdle Exercise Testing Workshop, Madrid, Spain, 11-12 July 2014. Neuromuscul Disord. 2015 Sep;25(9):739-45. doi: 10.1016/j.nmd.2015.05.009. PMID: 26159598 Carr AS, Pelayo-Negro AL, Jaunmuktane Z, et al. Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy. Neuromuscul Disord. 2015 Jun;25(6):511-5. doi: 10.1016/j.nmd.2015.02.001. PMID: 25819286 Brady S, Godfrey R, Scalco RS, Quinlivan RM. Emotionally-intense situations can result in rhabdomyolysis in McArdle disease. BMJ Case Rep. 2014 Oct 7;2014. pii: bcr2013203272. doi: 10.1136/bcr-2013-203272. PMID: 25293680

20 | P a g e Brady S, Melath S, Scalco RS, Penn H. Fatal cardiac involvement complicating antisynthetase syndrome. BMJ Case Rep. 2014 Aug 25;2014. pii: bcr2014204409. doi: 10.1136/bcr-2014-204409. PMID: 25155488 Scalco RS, Chatfield S, Godfrey R, et al. From exercise intolerance to functional improvement: the second wind phenomenon in the identification of McArdle disease. Arq Neuropsiquiatr. 2014 Jul;72(7):538-41. PMID: 25054987

Next destination: Apply for Post-doc in Translational Research

Year 4 non-clinical

Louise King

Start Date: Sept 2013 PhD Project Title: Mitophagy deficiencies in mitochondrial DNA disease Supervisors: Helene Plun-Favreau, Professor Mike Hanna and Dr Mary Sweeney Funding source: MRC Centre Grant Length of studentship: 4 years

Project Description: Mitochondrial DNA (mtDNA) mutations are associated with numerous severe disorders, which primarily affect muscle and neural tissues. The clinical severity of patients is highly dependent on the proportion of mutant mtDNA present in affected tissues; therefore maintaining mitochondrial quality control processes is essential. Mitophagy is the process of selective mitochondrial degradation that occurs to maintain efficient synthesis of ATP in the cell and avoids the toxic accumulation of damaged mitochondria, and it has been suggested that mtDNA damage can induce this process. We aim to characterize the effect of particular mtDNA mutations, involving different aspects of oxidative phosphorylation, on the process of mitophagy.

Significant Publications: A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis. Habbout K, Poulin H, Rivier F, Giuliano S, Sternberg D, Fontaine B, Eymard B, Morales RJ, Echenne B, King L, Hanna MG, Männikkö R, Chahine M, Nicole S, Bendahhou S. Neurology. 2016 Jan 12;86(2):161-9. doi: 10.1212/WNL.0000000000002264. Epub 2015 Dec 11. PMID: 26659129

Andreea Manole

21 | P a g e Start Date: Sep 2013 PhD Project Title: Genetic and Functional Investigation of an Inherited Neuropathy and a Channelopathy: Brown-Vialetto-Van Laere Syndrome and Episodic ataxia 1 Supervisors: Professor Henry Houlden, Professor Dimitri Kullmann and Professor Mike Hanna Funding source: MRC Centre Length of studentship: 4 years

Project Description: During my PhD I will reprogram fibroblasts from patients with episodic ataxia 1, a disease that arises as a result of mutations in a type of potassium channels, into human induced pluripotent stem cells. I will then characterize these cells by looking at pluripotency markers, karyotype and identity. Finally I will differentiate them into cortical neurons, describe their properties and treat them for the disease.

Significant Publications: Severe axonal neuropathy is a late manifestation of SPG11 Manole A, Chelban V, Haridy N A, Berardo A, Reilly MM , Houlden H J Neurol. 2016 in press Genetic and phenotypic characterization of complex hereditary spastic paraplegia. Kara E, Tucci A, Manzoni C, Lynch DS, Elpidorou M, Bettencourt C, Chelban V, Manole A, Hamed SA, Haridy NA, Federoff M, Preza E, Hughes D, Pittman A, Jaunmuktane Z, Brandner S, Xiromerisiou G, Wiethoff S, Schottlaender L, Proukakis C, Morris H, Warner T, Bhatia KP, Korlipara LV, Singleton AB, Hardy J, Wood NW, Lewis PA, Houlden H. Brain. 2016 Jul;139(Pt 7):1904-18. doi: 10.1093/brain/aww111. Epub 2016 May 23. PMID: 27217339 A novel KCNA1 mutation in a family with episodic ataxia and malignant hyperthermia. Mestre TA, Manole A, MacDonald H, Riazi S, Kraeva N, Hanna MG, Lang AE, Männikkö R, Yoon G. Neurogenetics. 2016 Jun 8. [Epub ahead of print] PMID: 27271339 Charcot-Marie-Tooth disease type 2C and scapuloperoneal muscular atrophy overlap syndrome in a patient with the R232C TRPV4 mutation. Koutsis G, Lynch D, Manole A, Karadima G, Reilly MM, Houlden H, Panas M. J Neurol. 2015 Aug;262(8):1972-5. doi: 10.1007/s00415-015-7800-x. Epub 2015 Jun 6. No abstract available. PMID: 26048687 Recent advances in bulbar syndromes: genetic causes and disease mechanisms. Manole A, Fratta P, Houlden H. Curr Opin Neurol. 2014 Oct;27(5):506-14. doi: 10.1097/WCO.0000000000000133. Review. PMID: 25159929 Riboflavin Transporter Deficiency Neuronopathy. Manole A, Houlden H. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Fong CT, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016. 2015 Jun 11. PMID: 26072523

Charlotte Spicer

22 | P a g e Start Date: Sep 2013

PhD Project Title: Investigating the effects of pharmacological up-regulation of the heat shock response in models of inclusion body myopathy Supervisors: Professor Linda Greensmith, Professor Michael Hanna Funding source: MRC Centre Grant Length of studentship: 4 years

Project Description: This PhD project involves characterising the histopathology in a transgenic mouse model of a hereditary form of inclusion body myopathy, which recapitulates many of the features of sporadic inclusion body myositis in muscle. We aim to examine the underlying pathomechanisms and changes in the muscle of the mutant mice. From this, we hope to obtain outcome measures which can be used to assess the therapeutic effects of Arimoclomol, a pharmacological co-inducer of the heat shock response. In addition, we have obtained fibroblasts from patients with VCP mutations and will examine whether these human cells also manifest any IBM-like pathology.

Significant Publications: Targeting protein homeostasis in sporadic inclusion body myositis. Ahmed M, Machado PM, Miller A, Spicer C, Herbelin L, He J, Noel J, Wang Y, McVey AL, Pasnoor M, Gallagher P, Statland J, Lu CH, Kalmar B, Brady S, Sethi H, Samandouras G, Parton M, Holton JL, Weston A, Collinson L, Taylor JP, Schiavo G, Hanna MG, Barohn RJ, Dimachkie MM, Greensmith L. Targeting protein homeostasis in sporadic inclusion body myositis. Sci Transl Med. 2016 Mar 23;8(331):331ra41. PubMed. PMID: 27009270

Michael Thor

Start Date: Sept 2013 PhD Project Title: Molecular and cellular pathological mechanisms of skeletal muscle channelopathies and related disorders Supervisors: Drs Roope Männikkö & Stephanie Schorge Funding source: MRC Centre Grant Length of studentship: 4 years

Project Description: Skeletal muscle channelopathies are a group of neuromuscular disorders where mutations disrupt the normal function of ion channels. I am interested in using electrophysiological techniques to study how pathogenic mutations in the NaV1.4 sodium and CaV1.1 calcium channels affect their function, and how they relate to the patient phenotype. By the end of this project, I hope to have significantly advanced our understanding of how mutations in related channels can lead to similar electrophysiological properties and clinical manifestations, as well as how different mutations within a single channel can lead to different diseases. This is a useful step towards predicting genotype- phenotype relationships in patients with channelopathies, to optimize therapeutic intervention and ultimately improve patient outcome.

23 | P a g e Significant Publications: Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy. Zaharieva IT, Thor MG, Oates EC, van Karnebeek C, Hendson G, Blom E, Witting N, Rasmussen M, Gabbett MT, Ravenscroft G, Sframeli M, Suetterlin K, Sarkozy A, D'Argenzio L, Hartley L, Matthews E, Pitt M, Vissing J, Ballegaard M, Krarup C, Slørdahl A, Halvorsen H, Ye XC, Zhang LH, Løkken N, Werlauff U, Abdelsayed M, Davis MR, Feng L, Phadke R, Sewry CA, Morgan JE, Laing NG, Vallance H, Ruben P, Hanna MG, Lewis S, Kamsteeg EJ, Männikkö R, Muntoni F. Brain. 2015 Dec 22. pii: awv352. [Epub ahead of print]

Emma Wilson

Start Date: Sept 2013 PhD Project Title: Cellular pathomechanisms and therapeutic strategies in Hereditary Sensory Neuropathy type 1 (HSN-1) Supervisors: Professor Linda Greensmith, Professor Mary Reilly, Dr Bernadett Kalmar Funding source: MRC Centre Grant Length of studentship: 4 years

Project Description: My project investigates an inherited disease of the peripheral nervous system called Hereditary Sensory Neuropathy type 1 (HSN-1). HSN-1 presents in patients with both motor and sensory dysfunction to differing extents. I use motor and sensory neuronal models to investigate the underlying pathomechanisms causing this disease and develop potential therapeutic treatments.

Emine Bagdatlioglu

Start date: September 2013 PhD Project Title: The application of MR imaging in the dystrophin deficient mouse brain: developing outcome measures for diagnostic and therapy development Funding source: MRC Centre Grant Supervisors: Professor Volker Straub & Professor Andrew Blamire

Project description: Duchenne muscular dystrophy (DMD), a fatal X-linked recessive disease, is the most common and best characterised form of muscular dystrophy. Although the dystrophin protein, encoded by the DMD gene, is most abundantly expressed in muscle, it is also expressed in the Central Nervous System (CNS). Intellectual impairment is recognised as a disease symptom in DMD and approximately one third of boys with DMD have some degree of cognitive deficit ranging

24 | P a g e from reduced verbal intelligence to severe autism. Our lack of knowledge about brain pathology in DMD is reflected in the limited number of studies of the CNS in mouse models of DMD, with hardly anything known about the anatomical or electrophysiological correlates in the mouse brain. The major focus of this project is the development and application of quantitative MRI, including diffusion tensor imaging (DTI) methods to access structural and metabolic brain pathology in mouse models of DMD. The imaging studies will be complemented by histological investigations and immunoanalysis of brain tissue. The overall aim of this research is to use MRI to develop imaging biomarkers that can be used for preclinical studies in DMD mouse models.

Marina Bartsakoulia

Start Date: September 2013 PhD Project Title: Mitochondrial translation deficiencies Supervisors: Professor Rita Horvath, Dr Veronika Boczonadi and Professor Patrick Chinnery Funding Source: Randerson Foundation Length of Studentship: 3 years (+ up to 1 year unfunded to write up)

Project Description: Mitochondrial disorders comprise a large group of heterogeneous disorders which are characterized by impairments in the cellular energy production. One of the great challenges of mitochondrial disease is the variety of clinical features present in patients. Mitochondrial disorders affect more than one organ leading to complex multisystem dysfunctions. Tissues, in which the metabolic demand is higher, such as skeletal muscle, neurons, liver or heart are typically affected. Mutations in both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) often lead to mitochondrial disorders. Hence, efficient mitochondrial function is critically dependent on concerted action of the two genomes. There is not much available to date to treat mitochondrial disease. Vitamin supplements, pharmacological agents and exercise therapy are common strategies used in individuals suffering from mitochondrial disorders. My project focuses on the reversibility and tissue specificity of mitochondrial translation deficiencies and therefore I will investigate the effect of L-cysteine and N- acetyl-cysteine supplementation on mitochondrial translation deficiencies and the tissue specificity presentation of some translational deficiencies.

Significant Publication: Bartsakoulia M, Müller SJ, Gomez-Duran A, Patrick Yu Wai Man, Boczonadi V, Horvath R: Cysteine Supplementation May be Beneficial in a Subgroup of Mitochondrial Translation Deficiencies, Journal of Neuromuscular Disorders 9/2016, DOI: 10.3233/JND-160178 Pyle A, Ramesh V, Bartsakoulia M, Boczonadi V, Gomez-Duran A, Herczegfalvi A, Blakely EL, Smertenko T, Duff J, Eglon G, Moore D, Yu-Wai-Man P, Douroudis K, Santibanez-Koref M, Griffin H, Lochmüller H, Karcagi V, Taylor RW, Chinnery PF, Horvath R.: Behr's Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in the C12orf65 Gene, Journal of Neuromuscular Diseases 2014;1(1):55-63, DOI: 10.3233/JND-140003

25 | P a g e Michele Giunta

Start Date: November 2013 PhD Project Title: Exosomal Protein Deficiencies: How Abnormal RNA Metabolism Results in Childhood-Onset Neurological Diseases Supervisors: Prof Rita Horvath, Prof. Patrick Chinnery, Dr. Veronika Boczonadi Funding Source: Marie-Curie “MEET” studentship Length of studentship: 3 years (+ up to 1 year unfunded to write up)

Project Description: Abnormal RNA metabolism is frequently associated with severe neurological disorders such as pontocerebellar hypoplasias and motor neuron disease. The exosome complex is an important RNA processing machinery within the cell and its correct functions are emerging as fundamental for correct neurodevelopment. My work aims to study the function and defects of the exosome complex which cause neurological disorders in patient cell lines and in zebrafish models of defective exosomal proteins.

Significant publications: Boczonadi V, Müller JS, Pyle A, Munkley J, Dor T, Quartararo J, Ferrero I, Karcagi V, Giunta M, ….. ,Chinnery PF, Edvardson S, Horvath R. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat Commun. 2014 Jul 3;5:4287. DOI:10.1038/ncomms5287 Müller JS, Giunta M, Horvath R. Exosomal Protein Deficiencies: How Abnormal RNA Metabolism Results in Childhood-Onset Neurological Diseases. J Neuromuscul Dis. 2015;2(Suppl 2):S31-S37. DOI: 10.3233/JND-150086 Giunta M, Edvardson S, Xu Y, Schuelke M, Gomez-Duran A, Boczonadi V, Elpeleg O, Müller JS, Horvath R. Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy. Hum Mol Genet. 2016 May 18. pii: ddw149. [Epub ahead of print] DOI:10.1093/hmg/ddw149

Ewen Sommerville

Start Date: Sept 2013 PhD Project Title: Identifying Novel Genes in Mitochondrial Disease Supervisors: Professor Robert W. Taylor and Dr Gráinne S. Gorman Funding source: MRC DTP Studentship Length of studentship: 3 years (+ up to 1 year unfunded to write up)

26 | P a g e Project Description: Whole exome sequencing (WES) is a targeted next-generation sequencing technology for the identification of all variants in the exons (coding regions) of all known genes. Mendelian mitochondrial disease has particularly benefitted from WES for attaining genetic diagnoses, due to the vast clinical and genetic heterogeneity of affected patients. My studentship aims to utilise WES to provide diagnoses for two mitochondrial disease patient cohorts with poor phenotype-genotype correlations:- (i) Adult-onset progressive external ophthalmoplegia (PEO) with multiple mitochondrial DNA (mtDNA) deletions. This mtDNA maintenance disorder is characterised by extraocular paresis and skeletal muscle restricted multiple mtDNA deletions. Affected patients present broad phenotypes ranging from indolent PEO to fatal multisystem PEO-plus. Furthermore, identification of pathogenic variants is further complicated since both autosomal dominant and recessive variants have been associated with this disorder. (ii) Early-onset mitochondrial translation disorders. This typically affects patients within the first decade of life and is characterised by multiple mitochondrial respiratory chain complex deficiencies. Both mtDNA maintenance and mitochondrial translation require the tight coordination of a vast set of nuclear-encoded proteins. Hence, WES allows the rapid identification of pathogenic variants by filtering of all associated nuclear-encoded genes. Following identification, characterisation of novel candidate disease genes seek to understand the underlying pathological mechanisms and to translate findings into potential therapeutic strategies.

Significant Publications: Ewen W. Sommerville, Yi Shiau Ng, Charlotte L. Alston, Cristina Dallabona, Micol Gilberti, Langping He, Charlotte Knowles, Sophie L. Chin, Andrew M. Schaefer, Gavin Falkous, David Murdoch, Cheryl Longman, Marianne de Visser, Laurence A. Bindoff, John M. Rawles, John C.S. Dean, Richard K. Petty, Maria E. Farrugia, Tobias B. Haack, Holger Prokisch, Robert McFarland, Douglass M. Turnbull, Claudia Donnini, Robert W. Taylor, Gráinne S. Gorman (2016) Clinical features, molecular heterogeneity and prognostic implications in YARS2-related mitochondrial myopathy. JAMA Neurol (In Press).

Renata Oliveira, Ewen W. Sommerville, Kyle Thompson, Joana Nunes, Angela Pyle, Manuela Grazina, Patrick F. Chinnery, Luísa Diogo, Paula Garcia, Robert W. Taylor (2016) Lethal neonatal LTBL associated with biallelic EARS2 variants: case report and review of the reported neuroradiological features. JIMD Rep DOI:10.1007/8904_2016_581 Robert Kopajtich, Thomas J. Nicholls, Joanna Rorbach, Metodi D. Metodiev, Peter Freisinger, Hanna Mandel, Arnaud Vanlander, Daniele Ghezzi, Rosalba Carrozzo, Robert W. Taylor, Klaus Marquard, Kei Murayama, Thomas Wieland, Thomas Schwarzmayr, Johannes A. Mayr, Sarah F. Pearce, Christopher A. Powell, Ann Saada, Akira Ohtake, Federica Invernizzi, Eleonora Lamantea, Ewen W. Sommerville, Angela Pyle, Patrick F. Chinnery, Ellen Crushell, Yasushi Okazaki, Masakazu Kohda, Yoshihito Kishita, Yoshimi Tokuzawa, Zahra Assouline, Marlène Rio, François Feillet, Bénédict Mousson de Camaret, Dominique Chretien, Arnold Munnich, Björn Menten, Tom Sante, Joél Smet, Luc Régal, Abraham Lorber, Asaad Khoury, Massimo Zeviani, Tim M. Strom, Thomas Meitinger, Enrico S. Bertini, Rudy Van Coster, Thomas Klopstock, Agnès Rötig, Tobias B. Haack, Michal Minczuk, Holger Prokisch (2014) Mutations in GTPBP3 cause a mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis, and encephalopathy. Am J Hum Genet 95(6): 708-720. DOI:10.1016/j.ajhg.2014.10.017 Ewen W. Sommerville, Patrick F. Chinnery, Gráinne S. Gorman, Robert W. Taylor (2014) Adult- onset Mendelian PEO Associated with Mitochondrial Disease. J Neuromuscul Dis 1(2): 119-133. DOI:10.3233/JND-140041

27 | P a g e Amy Vincent

Start date: September 2013 PhD Project Title: Investigating mitochondrial dysfunction in mitochondrial myopathy and other myopathies Supervisors: Professor Sir Doug Turnbull, Professor Rob Taylor, Dr Rita Barresi Funding Source: MRC DTP studentship Length of studentship: 3 years (+ up to 1 year unfunded to write up)

Project Description: Mitochondrial DNA mutations and mitochondrial respiratory chain deficiency arise in a mosaic pattern within the skeletal muscle of patients with mitochondrial myopathy. However, they are also found in a number of other myopathies and in aging skeletal muscle. My work looks to investigate mitochondria dysfunction and associated pathogenic mechanisms in both mitochondrial and other myopathies. This is being approached from three angles: 1) Characterising mitochondrial dysfunction in myofibrillar myopathy, dysferlinopathy and centronucelar myopathy and looking for potential links to disease pathology. 2) Attempting to understand mechanisms and factors effecting clonal expansion of mitochondrial DNA mutations. 3) Looking to make links between mitochondrial morphology, ultrastructure and function.

Significant publications: Amy E. Vincent, John P. Grady, Mariana C. Rocha, Charlotte L. Alston, Karolina A. Rygiel, Rita Barresi, Robert W. Taylor, Doug M. Turnbull: Mitochondrial dysfunction in myofibrillar myopathy. Neuromuscular Disorders 08/2016; DOI:10.1016/j.nmd.2016.08.004 (in press) Amy E. Vincent, Hannah S. Rosa, Charlotte L. Alston, John P. Grady, Karolina A. Rygiel, Mariana C. Rocha Rita Barresi, Robert W. Taylor, Doug M. Turnbull: Dysferlin mutations and mitochondrial dysfunction. Neuromuscular Disorders 08/2016; DOI:10.1016/j.nmd.2016.08.004 (in press) Amy E Vincent, Yi Shiau Ng, Kathryn White, Tracey Davey, Carmen Mannella, Gavin Falkous, Catherine Feeney, Andrew M Schaefer, Robert Mcfarland, Grainne S Gorman, Robert W Taylor, Doug M Turnbull, Martin Picard: The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy. Scientific Reports 09/2016; 6. DOI:10.1038/srep30610 Martin Picard, Amy E Vincent, Doug M. Turnbull: Expanding Our Understanding of mtDNA Deletions. Cell Metabolism 07/2016; 24(1). DOI:10.1016/j.cmet.2016.06.024 Virgilio J. J. Cadete, Sonia Deschênes, Alexanne Cuillerier, François Brisebois, Ayumu Sugiura, Amy Vincent, Doug Turnbull, Martin Picard, Heidi M. McBride, Yan Burelle: Formation of Mitchondrial-derived vesicles is an active and physiologically relevant mitochondrial quality control process in the cardiac system. The Journal of Physiology 06/2016; DOI:10.1113/JP272703 Karolina A. Rygiel, Helen A. Tuppen, John P. Grady, Amy Vincent, Emma L. Blakely, Amy K. Reeve, Robert W. Taylor, Martin Picard, James Miller, Doug M. Turnbull: Complex mitochondrial DNA rearrangements in individual cells from patients with sporadic inclusion body myositis. Nucleic Acids Research 04/2016; 44(11). DOI:10.1093/nar/gkw382 Mariana C Rocha, John P Grady, Anne Grünewald, Amy Vincent, Philip F Dobson, Robert W Taylor, Doug M Turnbull, Karolina A Rygiel: A novel immunofluorescent assay to investigate oxidative phosphorylation deficiency in mitochondrial myopathy: Understanding mechanisms and improving diagnosis. Scientific Reports 10/2015; 5. DOI:10.1038/srep15037

28 | P a g e Yasmin Issop

Start Date: September 2013 PhD Project Title: A GFPT1 Deficient Mouse Model of Congenital Myasthenic Syndrome Supervisors: Professor Hanns Lochmüller & Dr Andreas Roos Funding source: MRC/Barbour Foundation Length of studentship: 3 years

Project Description: Congenital Myasthenic Syndromes (CMS) are inherited neuromuscular transmission defects characterised by fluctuating muscle weakness and fatigability. CMS differ in terms of severity, course of the disease, inheritance pattern and treatment options depending on the underlying molecular defect, making them a paradigm for individualized medicine. We have identified mutations in the GFPT1 gene giving rise to a novel form of CMS. GFPT1 encodes a ubiquitous protein in the hexosamine pathway which yields precursor substrates required for protein and lipid glycosylation. The aims of this project are to breed and characterise a Gfpt1 knockout mouse model. We will investigate the consequence of GFPT1 deficiency on the glycosylation of skeletal muscle and neuromuscular junction proteins in mice. We will determine whether GFPT1 deficiency results in a modification of glycosyl residues on these proteins and whether this affects acetylcholine receptor clustering at the neuromuscular junction.

Visiting fellows

Pedro J Tomaselli

Start Date: Oct 2014 Clinical Research Fellow Supervisor: Prof Mary M Reilly Project: Next generation sequencing use to determine genetic causes of hereditary neuropathy

Project description: Charcot-Marie-Tooth (CMT) disease is a genetically heterogeneous group of hereditary disease affecting the sensory and motor nerves in the peripheral nervous system. Clinically it is characterized by slowly progressive weakness, and numbness affecting the upper and lower limbs in a length-dependent fashion. It is caused by mutations in more than 80 different genes. The high- throughput sequencing technologies (multigene target panels and whole exome sequencing) have

29 | P a g e revolutionized the approach to all hereditary diseases. These are increasingly methods used in clinical practice and have a certain application value in the hereditary neuropathy field as well. Therefore, these methods generate a massive amount of data, and sometimes is difficulty to achieve a definitive molecular diagnosis because of the complexity of interpreting new variants and/or the genetic heterogeneity that is associated with these hereditary neuropathies. We sought to explore the application value of next-generation sequencing techniques in the diagnosis of CMT, and determine the efficacy of these methods in clinical practice, whether they are cost-effective.

Significant Publications whilst at Centre: Horga A, Cottenie E, Tomaselli PJ, Rojas-García R, Salvado M, Villarreal-Pérez L, Gamez J, Márquez-Infante C, Houlden H, Reilly MM. J Neurol. Absence of HINT1 mutations in a UK and Spanish cohort of patients with inherited neuropathies. 2015 Aug;262(8):1984-6. PMID: 26194197 Tomaselli PJ, Rossor AM, Polke JM, Poh R, Blake J, Reilly MM. Semi-dominant mutations in MFN2-related neuropathy and implications for genetic counselling. J Peripher Nerv Syst. 2016 Mar;21(1):52-4. PMID: 26194197

Completing research Status / awaiting PhD viva

Matthew Evans

Start Date: April 2013 PhD Project Title: Development and application of Neuromuscular MRI Supervisors: Professor Mary M Reilly, Dr John Thornton, Professor Michael Hanna Funding source: Host matched funding (UCLH BRC) Length of studentship: 3 years

Project Description: As we move closer toward clinical trials of treatments for inherited neuromuscular diseases, the need for a valid, reliable and responsive outcome measure becomes increasingly important. My research is focussed on further refining quantitative MRI as an outcome measure in patients with neuromuscular disease, and the application of improved MRI analysis methods to both the cross sectional and longitudinal assessment of various neuromuscular diseases currently being studied at the MRC Centre including inclusion body myositis and Charcot-Marie-Tooth disease.

Significant Publications: Evans M, Manji H. Progress in Peripheral nerve disease research in the last two years. J Neurol (2013) 260:3188–3192. DOI 10.1007/s00415-013-7121-x MRB Evans, H Manji. Neurology in Africa – Howlett. A Book review. J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp-2014-308919. Matthew RB Evans, Jasper M Morrow. The pupillary examination. Br J Hosp Med (Lond). 2015 Apr;76(4):C50-4. doi: 10.12968/hmed.2015.76.4.C50. Matthew R B Evans, Matilde Laurá, Hoskote Chandrashekar, Mary M Reilly. Cervical spinal cord compression complicating the clinical course of Charcot-Marie-Tooth type 1. BMJ Case Rep. 2015. doi:10.1136/bcr-2015-213486.

30 | P a g e Rossor AM, Evans MR, Reilly MM. A practical approach to the genetic neuropathies. Pract Neurol. 2015 Apr 21. pii: practneurol-2015-001095. doi: 10.1136/practneurol-2015-001095. Carr AS, Pelayo-Negro AL, Jaunmuktane Z, Scalco RS, Hutt D, Evans MR, Heally E, Brandner S, Holton J, Blake J, Whelan CJ, Wechalekar AD, Gillmore JD, Hawkins PN, Reilly MM. Transthyretin V122I amyloidosis with clinical and histological evidence of amyloid neuropathy and myopathy. Neuromuscul Disord. 2015 Feb 14. pii: S0960-8966(15)00036-X. doi: 10.1016/j.nmd.2015.02.001. Carr AS, Pelayo-Negro AL, Evans MR, Laurà M, Blake J, Stancanelli C, Iodice V, Wechalekar AD, Whelan CJ, Gillmore JD, Hawkins PN, Reilly MM. A study of the neuropathy associated with transthyretin amyloidosis (ATTR) in the UK. J Neurol Neurosurg Psychiatry. 2015 Aug 4. pii: jnnp- 2015-310907. doi: 10.1136/jnnp-2015-310907.

Alex Horga

PhD Dates: 2011- 2015 PhD Title: Peripheral neuropathy and mitochondrial disease Supervisors: Professor Mary M Reilly & Professor Michael Hanna Funding source: NCG mitochondrial disease service (prev. funding provided by Caja Madrid Fundacion) Length of studentship: 2 yrs (NCG) Project Description: Dr Horga is a clinical research fellow undertaking a PhD in peripheral neuropathy and mitochondrial disease with Professor Reilly and Professor Hanna. He has completed a clinical study on peripheral neuropathy in patients with progressive external ophthalmoplegia and is currently working with whole-exome sequencing to determine the genetic basis of inherited neuropathies and mitochondrial diseases.

Publications whilst at MRC Centre: Horga A, Pitceathly RDS, Blake JC, Woodward CE, Zapater P, Plant GT, Houlden H, Sweeney MG, Hanna MG, Reilly MM. Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia. [in preparation] Liu Y-T, Laura M, Hersheson J, Horga A, Jaunmuktane Z, Brandner S, Pittman A, Hughes D, Polke JM, Sweeney MG, Proukakis C, Janssen JC, Auer-Grumbach M, Zuchner S, Shields K, Reilly MM, Houlden H. Extended phenotypic spectrum of KIF5A mutations: from spastic paraplegia to axonal neuropathy. Neurology [in press] 2013 Horga A, Raja Rayan DL, Matthews E, Sud R, Fialho D, Durran SCM, Burge JA, Portaro S, Davis MB, Haworth A, Hanna MG. Prevalence study of genetically–defined skeletal muscle channelopathies in England. Neurology 2013;80(16):1472-1475. Pérez-Miralles F, Sastre-Garriga J, Tintoré M, Nos C, Perkal H, Río J, Edo MC, Horga A, Castilló J, Auger C, Huerga E, Rovira A, Montalban X. Clinical impact of early brain atrophy in clinically isolated syndromes. Mult Scler 2013 May 7 [Epub ahead of print] Vidal-Jordana A, Sastre-Garriga J, Pérez-Miralles F, Tur C, Tintoré M, Horga A, Auger C, Río J, Nos C, Edo MC, Arévalo MJ, Castilló J, Rovira A, Montalban X. Early pseudoatrophy on natalizumab is due to white matter volume changes. Mult Scler 2013 Jan 14 [Epub ahead of print] 2012

31 | P a g e Costa C, Arrambide A, Tintoré M, Castilló J, Sastre-Garriga J, Tur C, Río J, Vidal-Jordana A, Auger C, Nos C, Rovira A, Comabella M, Horga A, Montalban X. Value of NMO-IgG determination at the time of presentation as CIS. Neurology 2012; 78(20):1608-1611. Cantó E, Reverter F, Morcillo-Suárez C, Matesanz F, Fernández O, Izquierdo G, Vandenbroeck K, Rodríguez-Antigüedad A, Urcelay E, Arroyo R, Otaegui D, Olascoaga J, Saiz A, Navarro A, Sánchez A, Domínguez C, Caminero A, Horga A, Tintoré M, Montalban X, Comabella M. Chitinase 3-like 1 plasma levels are increased in A. Horga 9 April 2013 patients with progressive forms of multiple sclerosis. Mult Scler 2012; 18(7): 983-990. 2011 Horga A, Castilló J, Río J, Tintoré M, Auger C, Sastre-Garriga J, Edo MC, Pérez-Miralles F, Tur C, Nos C, Huerga E, Comabella M, Rovira A, Montalban X. An observational study of the effectiveness and safety of natalizumab in the treatment of multiple sclerosis. Rev Neurol 2011; 56(6): 321-330. Horga A, Tintoré M. Natalizumab in the treatment of relapsing-remitting multiple sclerosis. Neurología 2011 26 (6), 357-368. Peiró AM, Climent L, Zapater P, Horga A, Horga JF. Ketanserin potentiates morphine-induced antinociception mediated by kappa-receptor activation. Pharmacol Res 2011; 64(1): 80-84.

Jasper Morrow

PhD dates: 2009 – 2014 PhD Title: Development of Quantitative MRI as an Outcome Measure in Neuromuscular Diseases Funding source: MRC Centre Grant (original) Length of studentship: 4 years Supervisors: Professor Michael Hanna, Professor Mary M Reilly and Professor Tarek Yousry Lack of sensitive outcome measures is a major obstacle to clinical trials in many neuromuscular diseases (NMD). Lower limb muscle MRI allows non-invasive visualisation of acute and chronic pathology in NMD. This thesis assessed the reliability, validity and responsiveness of quantitative MRI in chronic neuromuscular diseases. A comprehensive quantitative MRI protocol of lower limb muscles was developed including T1, T2, fat fraction and magnetisation transfer ratio (MTR) measurements. The protocol was assessed for reliability and sensitivity to physiological variation in 47 healthy volunteers with 15 rescanned at a two week interval. This protocol was then performed together with detailed clinical assessments and isokinetic/isometric dynamometry in 20 patients with inclusion body myositis (IBM), 20 patients with Charcot-Marie-Tooth disease (CMT) and matched health volunteers twice at a 12 month interval. In the healthy volunteers, the inter-scan and inter-observer reliability was high (ICC 0.62-0.99) despite small observed physiological variation of between subjects. Fat fraction, T2 and MTR showed significant correlations with subject age in thigh and calf muscles and with subject weight in thigh muscles whereas gender did not influence quantitative parameters. Cross-sectional analysis showed strong correlations with both muscle strength and clinical severity measures demonstrating validity of MRI measurements as outcome measures. Longitudinal assessment demonstrated that excellent sensitivity to change of MRI measures; in particular muscle fat fraction quantification exceeded that of myometry and clinical measurements with standardised response mean over 12 months of 1.1 in IBM and 0.8 in CMT indicating a high level of responsiveness. Annual change in fat fraction could be predicted based on baseline MRI measurements, providing the opportunity to

32 | P a g e improve SRM further. This thesis demonstrates the reliability, validity and responsiveness of quantitative MRI as an outcome measure providing a comprehensive practical protocol for clinical trials in NMD.

Significant Publications: Finlayson S, Morrow JM, Rodriguez Cruz PM, Sinclair CDJ, Fischmann A, Thornton JS, Knight S, Norbury R, White M, Al-Hajjar M, Carboni N, Jayawant S, Robb SA, Yousry TA, Beeson D, Palace J. Muscle MRI in congenital myasthenic syndromes. Muscle Nerve. 2016 Jan 20; PMID: 26789134 Pitceathly RDS, Morrow JM, Sinclair CDJ, Woodward C, Sweeney MG, Rahman S, Plant GT, Ali N, Bremner F, Davagnanam I, Yousry TA, Hanna MG, Thornton JS. Extra-ocular muscle MRI in genetically-defined mitochondrial disease. Eur Radiol. 2016 Jan;26(1):130–137. PMID: 25994195 Morrow JM, Sinclair CDJ, Fischmann A, Machado PM, Reilly MM, Yousry TA, Thornton JS, Hanna MG. MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study. Lancet Neurol. 2016 Jan;15(1):65–77. PMCID: PMC4672173 Suetterlin KJ, Bugiardini E, Kaski JP, Morrow JM, Matthews E, Hanna MG, Fialho D. Long-term Safety and Efficacy of Mexiletine for Patients With Skeletal Muscle Channelopathies. JAMA Neurol. 2015 Dec 1;72(12):1531–1533. PMID: 26658970 Morrow JM, Reilly MM. Early detection of nerve injury in transthyretin-related familial amyloid polyneuropathy. Brain. 2015 Mar;138(Pt 3):507–509. PMID: 25713400 Machado PM, Ahmed M, Brady S, Gang Q, Healy E, Morrow JM, Wallace AC, Dewar L, Ramdharry G, Parton M, Holton JL, Houlden H, Greensmith L, Hanna MG. Ongoing developments in sporadic inclusion body myositis. Curr Rheumatol Rep. 2014 Dec;16(12):477. PMCID: PMC4233319 Morrow JM, Sinclair CDJ, Fischmann A, Reilly MM, Hanna MG, Yousry TA, Thornton JS. Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers. Eur Radiol. 2014 Jul;24(7):1610–1620. PMCID: PMC4046083 Willis TA, Hollingsworth KG, Coombs A, Sveen M-L, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CDJ, Thornton JS, Bushby K, Lochmüller H, Hanna MG, Hogrel J-Y, Carlier PG, Vissing J, Straub V. Quantitative magnetic resonance imaging in limb- girdle muscular dystrophy 2I: a multinational cross-sectional study. PLoS ONE. 2014;9(2):e90377. PMCID: PMC3938727 Fischmann A, Morrow JM, Sinclair CDJ, Reilly MM, Hanna MG, Yousry T, Thornton JS. Improved anatomical reproducibility in quantitative lower-limb muscle MRI. J Magn Reson Imaging. 2013 Oct 7; PMID: 24123788 Morrow JM, Matthews E, Raja Rayan DL, Fischmann A, Sinclair CDJ, Reilly MM, Thornton JS, Hanna MG, Yousry TA. Muscle MRI reveals distinct abnormalities in genetically proven non- dystrophic myotonias. Neuromuscul Disord. 2013 Aug;23(8):637–646. PMID: 23810313 Morrow JM, Reilly MM, Hanna MG. Reliability and accuracy of skeletal muscle imaging in limb-girdle muscular dystrophies. Neurology. 2013 Jun 11;80(24):2276. PMID: 23905174 Cortese A, Machado P, Morrow J, Dewar L, Hiscock A, Miller A, Brady S, Hilton-Jones D, Parton M, Hanna MG. Longitudinal observational study of sporadic inclusion body myositis: implications for clinical trials. Neuromuscul Disord. 2013 May;23(5):404–412. PMID: 23489664 Morrow JM, Pitceathly RDS, Quinlivan RM, Yousry TA. Muscle MRI in Bethlem myopathy. Case Reports. 2013 Apr 16;2013(apr16 1):bcr2013008596–bcr2013008596. Cottenie E, Menezes MP, Rossor AM, Morrow JM, Yousry TA, Dick DJ, Anderson JR, Jaunmuktane Z, Brandner S, Blake JC, Houlden H, Reilly MM. Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy. Neuromuscul Disord. 2013 Mar 12; PMID: 23489662 Pitceathly RDS, Tomlinson SE, Hargreaves I, Bhardwaj N, Holton JL, Morrow JM, Evans J, Smith C, Fratter C, Woodward CE, Sweeney MG, Rahman S, Hanna MG. Distal myopathy with cachexia: an unrecognised phenotype caused by dominantly-inherited mitochondrial polymerase γ mutations. J Neurol Neurosurg Psychiatr. 2013 Jan;84(1):107–110. PMID: 22933815 Willis TA, Hollingsworth KG, Coombs A, Sveen M-L, Andersen S, Stojkovic T, Eagle M, Mayhew A, de Sousa PL, Dewar L, Morrow JM, Sinclair CDJ, Thornton JS, Bushby K, Lochmüller H, Hanna MG, Hogrel J-Y, Carlier PG, Vissing J, Straub V. Quantitative Muscle MRI as an Assessment Tool

33 | P a g e for Monitoring Disease Progression in LGMD2I: A Multicentre Longitudinal Study. PLoS ONE. 2013;8(8):e70993. PMID: 23967145 Sinclair CDJ, Morrow JM, Hanna MG, Reilly MM, Yousry TA, Golay X, Thornton JS. Correcting radiofrequency inhomogeneity effects in skeletal muscle magnetisation transfer maps. NMR Biomed. 2012 Feb;25(2):262–270. PMID: 21796708 Sinclair CDJ, Morrow JM, Miranda MA, Davagnanam I, Cowley PC, Mehta H, Hanna MG, Koltzenburg M, Yousry TA, Reilly MM, Thornton JS. Skeletal muscle MRI magnetisation transfer ratio reflects clinical severity in peripheral neuropathies. J Neurol Neurosurg Psychiatr. 2012 Jan;83(1):29–32. PMID: 21613652 Sinclair CDJ, Miranda MA, Cowley P, Morrow JM, Davagnanam I, Mehta H, Hanna MG, Koltzenburg M, Reilly MM, Yousry TA, Thornton JS. MRI shows increased sciatic nerve cross sectional area in inherited and inflammatory neuropathies. J Neurol Neurosurg Psychiatr. 2011 Nov;82(11):1283–1286. PMID: 20971754 Morrow JM, Reilly MM. The Babinski sign. Br J Hosp Med (Lond). 2011 Oct;72(10):M157–159. PMID: 22041660

Next Destination: Consultant Neurologist, National Hospital for Neurology & Neurosurgery, & Lister Hospital, Stevenage

Qiang Gang

Start Date: Sept 2012 PhD Project Title: Genetic investigations of sporadic inclusion body myositis and myopathies with structural abnormalities and protein aggregates in muscle Supervisors: Professor Henry Houlden, Professor Michael Hanna & Dr Conceição Bettencourt Funding source: Host Impact (UCL) Length of studentship: 3 years

Project Description: Using whole-exome sequencing to investigate the pathogenesis of sporadic inclusion body myositis (IBM) and tubular aggregate myopathies (TAM). Both diseases are rare and the causes are unknown, and it is suggested that genetic factors might be involved in the disease process. Whole- exome sequencing is an advanced and cost-efficient approach to explore the genetic changes of the whole protein-coding region. We aim to identify the genetic risk factors associated with sporadic IBM and the disease-causing genes for TAM, and to improve our understanding of these diseases.

Significant Publications: Rare variants in SQSTM1 and VCP genes and risk of sporadic inclusion body myositis. Gang Q, Bettencourt C, Machado PM, Brady S, Holton JL, Pittman AM, Hughes D, Healy E, Parton M, Hilton-Jones D, Shieh PB, Zanoteli E, Camargo LV, De Paepe B, De Bleecker J, Shaibani A, Ripolone M, Violano R, Moggio M, Barohn RJ, Dimachkie MM, Mora M, Mantegazza R, Zanotti S, Singleton AB, Hanna MG, Houlden H; Muscle Study Group and the International IBM Genetics Consortium. 2016 (Accepted by Neurobiology of Aging) The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis.

34 | P a g e Gang Q, Bettencourt C, Machado PM, Fox Z, Brady S, Healy E, Parton M, Holton JL, Hilton-Jones D, Shieh PB, Zanoteli E, De Paepe B, De Bleecker J, Shaibani A, Ripolone M, Violano R, Moggio M, Barohn RJ, Dimachkie MM, Mora M, Mantegazza R, Zanotti S, Hanna MG, Houlden H; Muscle Study Group and the International IBM Genetics Consortium. Neurobiol Aging. 2015 Apr;36(4):1766. PMID:25670332 Genetic advances in sporadic inclusion body myositis. Gang Q, Bettencourt C, Houlden H, Hanna MG, Machado PM. Curr Opin. 2015 Nov;27(6):586- 94.PMID:26335925 Sporadic inclusion body myositis: the genetic contributions to the pathogenesis. Gang Q, Bettencourt C, Machado P, Hanna MG, Houlden H. Orphanet J Rare. 2014 Jun 19;9:88. PMID:24948216

Co-author publication: Ongoing developments in sporadic inclusion body myositis. Machado PM, Ahmed M, Brady S, Gang Q, Healy E, Morrow JM, Wallace AC, Dewar L, Ramdharry G, Parton M, Holton JL, Houlden H, Greensmith L, Hanna MG. Curr Rheumatol Rep. 2014 Dec;16(12):477.PMID:25399751

Next destination: Clinical training

Neta Amior

Start Date: Sept 2010 (currently in CRS) PhD Project Title: Developing models to study the mechanisms of weakness and myotonia in Periodic Paralysis Supervisors: Professor Michael Duchen and Professor Mike Hanna Funding source: Host Impact (UCL) Length of studentship: 3 years (+ 1 yr extended funding)

Project Description: Periodic paralysis (PP) is a disorder caused by mutations of skeletal voltage gated ion channels, characterised by episodic attacks of paralysis. Although these eventually subside, patients develop progressive muscle weakness and frequently, myopathy. The relationship between this progression and the associated mutations is not understood. I propose that the longer term defect might result from disordered calcium signalling and its impact on mitochondrial function. I therefore sought disease models in order to study these aspects of muscle signalling. These were: A model derived from patients: Patient derived fibroblasts were virally transduced with MyoD to generate myoblasts, which were differentiated into myotubes. This process proved too inefficient to collect adequate data. A pharmacological model: generated by treating neonatal rat myotube cultures with barium and low extracellular potassium to simulate attacks of PP. The model was validated using membrane potential sensitive dyes and by electrophysiological techniques. Treated cultures displayed more frequent spontaneous calcium fluctuations. Mitochondrial membrane potential was not affected by the treatment, but expression of TFAM, a regulator of mitochondrial transcription, was upregulated, suggesting activation of retrograde signalling pathways. A mouse model: collaborators at MRC Harwell generated mice carrying a mutation (c.1744A>G; p.Ile582Val) equivalent to a novel point mutation in SCN4A, one of the ion channel genes associated with PP. Measurements in-vivo established that affected mice show muscle weakness

35 | P a g e and delayed fatigue during tetanic responses. Calcium handling and mitochondrial function were analysed in single isolated myofibres. Calcium handling was not affected, however control fibres typically had a bigger mitochondrial membrane potential and more interfibrillar mitochondria, indicating that mitochondrial bioenergetics were affected. I describe several approaches that could be used to investigate the progressive weakness and myopathy in PP, and assess the relative merits of each approach.

Significant Publications: Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis. / Corrochano, Silvia; Männikkö, Roope; Joyce, Peter I.; McGoldrick, Philip; Wettstein, Jessica; Lassi, Glenda; Rayan, Dipa L Raja; Blanco, Gonzalo; Quinn, Colin; Liavas, Andrianos; Lionikas, Arimantas; Amior, Neta; Dick, James; Healy, Estelle G.; Stewart, Michelle; Carter, Sarah; Hutchinson, Marie; Bentley, Liz; Fratta, Pietro; Cortese, Andrea; Cox, Roger; Brown, Steve D. M.; Tucci, Valter; Wackerhage, Henning; Amato, Anthony A.; Greensmith, Linda; Koltzenburg, Martin; Hanna, Michael G.; Acevedo-Arozena, Abraham. In: Brain, Vol. 137, No. 12, 01.12.2014, p. 3171- 3185.

36 | P a g e Appendix 7. Centre clinical trials, natural history studies and core translational activity reports

Current UK Neuromuscular Clinical Trials

MRC Centre CTIMPs Set-up Phase trials

1. Mesoangioblast-mediated exon 51 skipping, based upon a single intra-muscular injection of five non ambulant DMD patients: a non-randomized, open label, phase I/IIa study Status: Set-up phase Sponsor: University of Manchester Funder: The Wellcome Trust CI: Dr. Imelda Hughes PI: Prof. Giulio Cossu

2. Multicentre, open-label, single arm study to evaluate long-term safety tolerability , and effectiveness of 10 mg/kg Olesoxime in patients with SMA Status: Set-up phase Sponsor/Funder: F. Hoffmann-La Roche Ltd PI: Dr Ros Quinlivan Target: 1-2

3. SIDEROS A phase III double-blind, randomised, placebo-Controlled study assessing the efficacy, safety and tolerability of Idebenone in patients with Duchenne Muscular Dystrophy receiving glucocorticoid Steroids Status: Set-up phase Sponsor/Funder: Santhera Pharmaceuticals (Switzerland) Limited PI: Dr Ros Quinlivan

4. A phase IIb/III of Arimoclomol in IBM Status: Set-up phase Planned start date: December 2016 Sponsor: UCL Funder: FDA/HeFce-HEIF PI: Professor Michael Hanna Recruitment target: 150 (distributed across no more than 11 sites in 2 countries)

5. A Phase 3b Open-label Extension Study to Evaluate the Safety and Efficacy of Aceneuramic Acid Extended-Release (Ace-ER) Tablets in Patients with GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM) Status: Set-up phase Sponsor: Ultragenyx CI/PI: Professor Hanns Lochmüller

6. A Phase III Double-blind, Randomized, Placebo-Controlled Study assessing the Efficacy, Safety and Tolerability of Idebenone in Patients with Duchenne Muscular Dystrophy Receiving Glucocorticoid steroids Status: Set-up phase Sponsor: Santhera Pharmaceuticals PI: Dr Michela Guglieri

1 | P a g e 7. A phase 3 randomized, multicenter, multinational, double-blinded study comparing the efficacy and safety of repeated biweekly infusions of neoGAA (GZ402666) and alglucosidase alfa in treatment-naïve patients with late onset Pompe disease Status: Set-up phase Sponsor: Sanofi Genzyme CI/PI: Professor Volker Straub Target: 0-1

8. Randomised, double blind, placebo controlled, multicentre study to evaluate the efficacy and safety of givinostat in ambulant patients with Duchenne Muscular Dystrophy Status: Set-up phase Sponsor: Italfarmaco PI: Dr Michela Guglieri

9. An Open-label Extension Study for Patients with Spinal Muscular Atrophy who Previously Participated in Investigational Studies of ISIS 396443 Status: Set-up phase Sponsor: ISIS Pharmaceuticals Newcastle PI: Professor Volker Straub Recruitment Target 2-4 London PI: Professor Muntoni Recruitment Target 2-4

10. A two part seamless multi-center randomized placebo controlled study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of RO7034067 in type 2 and 3 spinal muscular atrophy patients Status: Set-up phase Sponsor: Roche CI/PI: Professor Hanns Lochmüller

11. A Double-Blind, Placebo-Controlled, Multi-Center Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients with Duchenne Muscular Dystrophy Status: Set-up phase Sponsor: Sarepta Therapeutics PI: Professor Volker Straub

12. A two-part seamless, multicentre, randomised, placebo-controlled double-blind study to investigate the safety tolerability, pharmacokinetics, pharmacodynamics and efficacy of RO7034067 in type 2 and 3 Spinal Muscular Atrophy Status: Set-up phase Sponsor: F. Hoffmann – La Roche Ltd Planned start date (if set-up phase): September PI: Prof Muntoni Recruitment target: 6-8

13. A two-part seamless, multicentre, randomised, placebo-controlled double-blind study to investigate the safety tolerability, pharmacokinetics, pharmacodynamics and efficacy of RO7034067 in infants with type 1 Spinal Muscular Atrophy Status: Set-up phase Sponsor: F. Hoffmann – La Roche Ltd Planned start date (if set-up phase): September PI: Prof Muntoni Recruitment target: 2-4

2 | P a g e MRC Centre CTIMPs Open Trials

STARTED POST JANUARY 2013

14. A Single-Blind, Phase 2 Study To Evaluate The Safety And Efficacy Of Tideglusib 400mg Or 1000mg For The Treatment Of Adolescent And Adult Congenital And Juvenile- Onset Myotonic Dystrophy Status: Open to recruitment Target: 16 Sponsor: AMO Pharma CI/PI: Professor Hanns Lochmüller Recruitment: 1

15. Multicentre, open-label, single arm study to evaluate long-term safety, tolerability, and effectiveness of 10 mg/kg Olesoxime in patients with SMA Status: Open to recruitment Target: 1-3 Sponsor: Roche CI: Professor Hanns Lochmüller PI: Dr Michela Guglieri Recruitment: 1

16. A Phase II Clinical Study to Assess the Activity and Safety of Utrophin Modulation with SMT C1100 in Ambulatory Paediatric Male Subjects with Duchenne Muscular Dystrophy (C11005) Status: Open to recruitment Total Trial Target: 1-3 Sponsor: Summit CI: Professor Muntoni PI: Dr Michela Guglieri Recruitment: 0

17. Observational outcomes in testosterone treatment of pubertal delay in Duchenne Muscular Dystrophy Status: Open to recruitment Sponsor: Newcastle upon Tyne NHS Hospitals Foundation Trust CI: Professor Volker Straub PI: Dr Michela Guglieri Recruitment target: 20; patients recruited: 10

18. A Phase III Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Sialic Acid Extended Release Tablets in Patients with GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM) Status: Open to recruitment Sponsor: Ultragenyx Newcastle: CI/PI: Professor Hanns Lochmüller Recruitment target: 20; patients recruited: 18

19. Phase Ib/II, double-blind, placebo-controlled, within-subject, dose escalation study to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of PF-06252616 administered to ambulatory boys with Duchenne Muscular Dystrophy. Status: Open to recruitment

3 | P a g e Sponsor/Funder: PFIZER Newcastle: CI: Dr Michela Guglieri PI: Dr Michela Guglieri Recruitment target: 3-5; Patients recruited: 4 London GOSH: PI: Professor Francesco Muntoni Recruitment target: 5; Patients recruited: 4

20. A Phase III, Randomized, Double-blind, Sham-Procedure Controlled Study to Assess the Clinical Efficacy and Safety of ISIS 396443 Administered Intrathecally in Patients with Infantile-onset Spinal Muscular Atrophy Status: Open to recruitment Sponsor/Funder: Ionis Pharmaceuticals (previously known as ISIS Pharmaceuticals) London GOSH PI: Professor Francesco Muntoni Recruitment target: 2-4; Patients recruited: 4 Newcastle: PI: Professor Volker Straub Recruitment target: 1; Patients recruited: 1

21. FOR-DMD Duchenne muscular dystrophy: double-blind randomized trial to find optimum steroid regimen (FOR-DMD) Status: Open to recruitment Sponsor: University of Rochester Funder: NIH Newcastle CI: Professor Kate Bushby PI: Professor Volker Straub Recruitment target: 11 ; Patients recruited: 11 London GOSH PI: Professor Francesco Muntoni Recruitment target: 4; recruited: 6

22. PTC124-GD-019 Open label An open-label study for previously treated Ataluren (PTC124) patients with nonsense mutation dystrophinopathy Status: Ongoing but closed to recruitment Sponsor& Funder: PTC Newcastle CI: Professor Kate Bushby PI: Dr Michela Guglieri Patients recruited: 11 London GOSH PI: Professor Francesco Muntoni Patients recruited: 8

23. A phase III efficacy & safety study of Ataluren (PTC124®) in patients with nonsense mutation dystrophinopathy (PTC Phase III) PTC124-GD-020-DMD Status: Ongoing but closed to recruitment Sponsor/Funder: PTC Newcastle CI: Professor Kate Bushby PI: Dr Michela Guglieri

4 | P a g e Patients recruited: 4 London GOSH PI: Professor Francesco Muntoni Patients recruited: 7

24. An Open-label, multicentre, multinational, ascending dose study of the safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeated biweekly infusions of neoGAA in naïve and alglucosidasealfa treated late-onset Pompe disease patients. Status: Ongoing but closed to recruitment Sponsor/Funder: Genzyme PI/CI: Professor Volker Straub Patients recruited: 1

25. A Phase II/III Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ISIS 420915 in Patients with Familial Amyloid Polyneuropathy Status: Ongoing but closed to recruitment Sponsor: Ionis Pharmaceuticals, Inc. UCL PI: Dr Carol Whelan (ION PI: Professor Mary M Reilly) Patients recruited: 6 Global recruitment target: 195

26. A Pilot Study of Valproate Sodium for McArdle Disease Status: Ongoing but closed to recruitment Sponsor: UCL Funder: Muscular Dystrophy UK PI: Dr Ros Quinlivan Recruitment target: 8; Patients recruited: 8

27. Bumetanide in HypoPP A randomised, double-blind, placebo-controlled, phase II clinical trial with a cross-over design assessing efficacy of a single dose of bumetanide in reducing focal attack severity in hypokalaemic periodic paralysis assessed using the McManis protocol Status: Open to recruitment Sponsor: UCL Funder: UCL Charities PI: Dr Doreen Fialho Recruitment target: 12; Patients recruited: 6

28. A Phase I/II, open-label, dose escalating with 48-week treatment study to assess the safety and tolerability, pharmacokinetics, pharmacodynamics and efficacy of PRO053 in subjects with Duchenne muscular dystrophy Status: Ongoing but closed to recruitment Sponsor & Funder: Prosensa CI: Professor Volker Straub Newcastle: PI: Professor Volker Straub Recruitment target: 3-5; Patients recruited: 1 London GOSH: PI: Professor Francesco Muntoni Recruitment target: 1-2; Patients recruited: 1

29. A 2-Part, Randomized, Double-Blind, Placebo-Controlled, Dose-Titration, Safety, Tolerability, and Pharmacokinetics Study (Part 1) Followed by an Open-Label Efficacy and

5 | P a g e Safety Evaluation (Part 2) of SRP-4053 in Patients with Duchenne Muscular Dystrophy (DMD) Amenable to Exon 53 Skipping. Status: Open to recruitment Sponsor: Sarepta, EU Grant London GOSH: CI/PI: Professor Francesco Muntoni Recruitment target: 12; Patients recruited: 10 Newcastle: PI: Professor Volker Straub Recruitment target: 12; Patients recruited: 6

30. A Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Multiple- Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO6885247 following 12 Weeks treatment in Adult and Paediatric Patients with Spinal Muscular Atrophy Status: On Hold Sponsor: F. Hoffmann-La Roche Ltd Newcastle: CI/PI: Professor Hanns Lochmüller Recruitment target: 7; Patients recruited: 4 London GOSH – not open yet PI: Professor Francesco Muntoni

31. A Phase III Extension Study of Ataluren (PTC124) in Patients with Nonsense Mutation Dystrophinopathy (PTC20e Status: Ongoing but closed to recruitment Sponsor PTC therapeutics Newcastle CI: Professor Kate Bushby PI: Dr Michela Guglieri Recruitment target: 4; Patients recruited: 4 London GOSH PI: Professor Francesco Muntoni Recruitment target: 6-9; Patients recruited: 8

32. A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Study to Assess the Safety and Efficacy of UX007 in Subjects with Glucose Transporter Type 1 Deficiency Syndrome Status: Ongoing Sponsor: Ultragenyx PI: Dr Rita Horvath Recruitment target: 3; patients recruited: 4

33. Long-term Safety and Efficacy Study of Deferiprone in Patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN)- TIRCON2012V1-EXT Status: Ongoing Sponsor: ApoPharma Inc. CI: Prof Patrick Chinnery PI: Dr Rita Horvath Recruitment target: 6; patients recruited: 2

34. A Feasibility Study of Bezafibrate in Mitochondrial Myopathy Status: Ongoing Sponsor: Newcastle upon Tyne Hospitals NHS Foundation Trust CI: Prof Patrick Chinnery

6 | P a g e PI: Prof Rita Horvath Recruitment target: 10 (gp 1 n=6, gp 2 n=4); patients recruited: 4

STARTED PRE JANUARY 2013

35. DMD Heart Protection Trial A double-blind randomised multi-centre, placebo-controlled trial of combined ACE-inhibitor and beta-blocker therapy in preventing the development of cardiomyopathy in genetically characterised males with DMD without echo-detectable left ventricular dysfunction Status: Ongoing but closed to recruitment Sponsor: Newcastle upon Tyne NHS Hospitals Foundation Trust Funder: British Heart Foundation Newcastle PI: Dr John Burke Recruitment target: 20-30; Patients recruited: 26 London GOSH PI: Professor Francesco Muntoni Recruitment target: 50-60; Patients recruited: 46

36. A randomized, double-blind, placebo-controlled trial of deferiprone in patients with pantothenate kinase-associated neurodegeneration (PKAN)- TIRCON2012V1 Status: Ongoing but closed to recruitment Sponsor: ApoPharma Inc. CI: Prof Patrick Chinnery PI: Dr Rita Horvath Recruitment target: 8; patients recruited: 8

MRC Centre CTIMPs Completed Trials

STARTED POST JANUARY 2013

37. A phase IIb, open-label study to assess the efficacy, safety, pharmacodynamics and pharmacokinetics of multiple doses of PRO045 in subjects with Duchenne muscular dystrophy (PRO045) Status: Completed Sponsor/Funder: Prosensa Newcastle CI/PI: Professor Volker Straub Patients recruited: 2 London GOSH PI: Professor Francesco Muntoni Patients recruited: 1

38. SMT C11003 A placebo-controlled, multi-centre, randomized, double-blind, 3-period dose escalation study to evaluate the PK and safety of SMT C1100 in paediatric patients with Duchenne muscular dystrophy (DMD) who follow a balanced diet Status: Completed Sponsor: Summit Corporation plc PI: Professor Francesco Muntoni Recruitment target: 4; Patients recruited: 4

7 | P a g e 39. A randomized, double-blind, placebo-controlled, multicenter, parallel group, dose- finding, pivotal, phase IIb/III study to evaluate the efficacy, safety and tolerability of intravenous BYM338 at 52 weeks on physical function, muscle strength, and mobility and additional long-term safety up to 2 years in patients with sporadic inclusion body myositis Status: Completed Sponsor/Funder: Novartis CI: Professor Michael Hanna PIs: Hector Chinoy; James Miller (recruited 15) Patients recruited: 44 (UK); 353 (Worldwide)

40. Extension of the CBYM338B2203 phase IIb/III study to evaluate the long-term efficacy, safety and tolerability of intravenous BYM338 in patients with sporadic inclusion body myositis Status: Completed Sponsor: UCL Funder: Novartis PI: Professor Michael Hanna UK Recruitment target: 26 patients Newcastle PI: Dr James Miller: Patients recruited: 9 London PI: Professor Michael Hanna Patients recruited: 7

41. PATH extension Study Multicentre, open-label extension study to investigate the long-term safety and efficacy of IgPro20 in maintenance treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in subjects completing study IgPro20_3004 Status: Completed Sponsor: CSL Behring PI: Dr Michael Lunn Recruitment target: 3; Patients recruited: 3

42. A double-blind, randomised, multicentre, placebo-controlled, parallel-group study to evaluate the efficacy and safety of fingolimod 0.5 mg administered orally once daily versus placebo in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) Status: Completed/Terminated for futility Sponsor: Novartis PI: Dr Michael Lunn Recruitment target: 1-2; Patients recruited: 2

43. GSK/Prosensa clinical trial in DMD boys with study drug GSK2402968 (GSK Extension Study) An open-label extension study of the long-term safety, tolerability and efficacy of GSK2402968 in subjects with Duchenne Muscular Dystrophy Status: Closed to recruitment/ Dosing suspended Sponsor: GlaxoSmithKline Funder: GlaxoSmithKline Newcastle CI/PI: Professor Volker Straub Target: 5 Recruitment: 5 London GOSH PI: Professor Francesco Muntoni Recruitment target: 8; Patients recruited: 8

8 | P a g e 44. SMT C1100 – A Phase I, Open-label, Single and Multiple Oral Dose, Safety, Tolerability and Pharmacokinetic Study in Paediatric Patients with Duchenne Muscular Dystrophy Status: Completed Sponsor & Funder: Summit London GOSH PI: Professor Francesco Muntoni Patients Recruited: 4 Ricotti V, et al. PLoS One. 2016 Apr 7;11(4). PMID: 27055247

STARTED PRE JANUARY 2013

45. Randomised double-blind placebo controlled trial of long-term ascorbic acid treatment in Charcot-Marie-Tooth disease type 1a Status: Completed Sponsor: University College London Funder: Muscular Dystrophy UK PI: Professor Mary M Reilly Recruitment target: 50; Patients recruited: 50 Pareyson D, et al. Lancet Neurology 2011 Apr;10(4):320-8. PMID: 21393063

46. Therapeutic trial of Mexiletine in Non-Dystrophic Myotonia A Phase II Randomised, Double-Blind, Placebo controlled, Cross-Over Study to Investigate the Efficacy of Mexiletine in Patients with Non-Dystrophic Myotonia Status: Completed Sponsor: University College London (UCL) Funder: Food and Drug Administration (FDA – USA) PI: Professor Michael Hanna Recruitment target: 15; Patients recruited: 14 Statland JM, et al. JAMA 2012 Oct 3;308(13):1357-65. PMID:23032552

The MRC Centre has been granted 'Orphan Medicinal Product' designation for Mexiletine for Non- Dystrophic Myotonia by the European Commission

47. A phase IIb efficacy and safety study of PTC124 in subjects with nonsense mutation mediated Duchenne and Becker muscular dystrophy Status: Completed Sponsor: PTC Therapeutics Funder: PTC Therapeutics Newcastle CI: Professor Kate Bushby London GOSH PI: Professor Francesco Muntoni Patients recruited: 11

48. Restoring dystrophin expression in Duchenne Muscular Dystrophy: a phase I/II clinical trial using AVI-4658 Status: Completed Sponsor: Imperial College London Funder: Department of Health (DoH) PI: Professor Francesco Muntoni Patients recruited: 8 Kinali M, et al. Lancet Neurology 2009 Oct;8(10):918-28. PMID:19713152

9 | P a g e 49. Dose-ranging study of AVI-4658 to induce dystrophin expression in selected Duchenne Muscular Dystrophy (DMD) patients – (Systemic study) Status: Completed Sponsor: AVI Biopharma Funder: Medical Research Council (MRC) and AVI Biopharma Newcastle: PI: Professor Kate Bushby London: PI: Professor Francesco Muntoni Patients recruited: 19 Cirak S, et al. Lancet. 2011 Aug 13;378(9791):595. PMID: 21784508

50. Eculizumab for Myasthenia Gravis A Randomised, Double-Blind, Placebo-controlled, Cross-over, Multicentre Study of Eculizumab in Patients with Generalised Myasthenia Gravis (GMG) who have Moderate to Severe Muscle Weakness Despite Treatment with Immunosupressants Status: Completed Sponsor/Funder: Alexion Pharmaceuticals, Inc. PI: Professor Dimitri Kullmann Howard JF Jr, et al. Muscle Nerve. 2013 Jul;48(1):76-84. PMID: 23512355

51. Arimoclomol for Sporadic Inclusion Body Myositis (IBM) A Randomised, Double-blinded, Placebo-controlled Pilot Study Assessing the Safety and Tolerability of Arimoclomol in Adult Patients with Sporadic Inclusion Body Myositis Status: Completed Sponsor: University College London (UCL) Funder: Arthritis Research UK and Myositis Support Group PI: Professor Michael Hanna Recruitment target: 12; Patients recruited: 12 Ahmed M, et al. Sci Transl Med. 2016 Mar 23;8(331):331. PMID: 27009270

52. Investigation of the ability of Otelixizumab to inhibit in vitro antigen-specific T cell responses from Myasthenia Gravis patients Status: Completed Sponsor/Funder: GlaxoSmithKline PI: Professor Dimitri Kullmann Recruitment target: 40; Patients recruited: 39

53. GSK/Prosensa clinical trial in DMD boys with study drug GSK2402968 (PRO051) A phase II, double-blind, exploratory, parallel-group, placebo-controlled clinical study to assess two dosing regimens of GSK2402968 for efficacy, safety, tolerability and pharmacokinetics in ambulant subjects with Duchenne muscular dystrophy Status: Completed Sponsor: GlaxoSmithKline Funder: GlaxoSmithKline Newcastle CI/PI: Professor Volker Straub Target: 4, Recruitment: 5 London GOSH PI: Professor Francesco Muntoni Recruitment target (UK): 8; Patients recruited (UK): 8 Voit T, et al. Lancet Neurol. 2014 Oct;13(10):987-96. PMID: 25209738

54. Therapeutic trial of lithium carbonate in MND/(LiCALS)

10 | P a g e A double-blind, randomised, placebo controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis Status: Completed Sponsor: University College London Hospitals NHS Foundation Trust Funder: Motor Neurone Disease Association, and NIHR UCL PI: Dr Richard Orrell Recruitment target: 22; Patients recruited: 22 Al-Chalabi A,et al. BMC Neurol. 2011 Sep 21;11:111 PMID: 21936930 UKMND-LiCALS Study Group, et al. Lancet Neurol. 2013 Apr;12(4):339-45. PMID: 23453347

55. LiCALS Open Label Extension LiCALS open label extension trial of lithium carbonate in amyotrophic lateral sclerosis Status: Completed Sponsor: University College London Hospitals NHS Foundation Trust Start date: March 2011 Funder: Motor Neurone Disease Association, and NIHR UCL PI: Dr Richard Orrell Recruitment target: 3; Patients recruited: 3 Results in Press

56. GSK1223249 in MND/ALS (the Nogo-A study) A Phase I, multi-centres, randomized, placebo-controlled, double-blind, single and repeat dose escalation of a drug to treat ALS Status: Completed Sponsor: Royal Free Hampstead NHS Trust Start date: September 2010 Funder: GlaxoSmithKline UCL PI: Dr Richard Orrell Recruitment target: 2; Patients recruited: 2 Meininger V, et al. PLoS One. 2014 May 19; 9(5):e97803. PMID: 24841795

57. HYP HOP: Dichlorphenamide vs. Placebo for Periodic Paralysis Double-blind, placebo-controlled, parallel group, phase III study comparing dichlorphenamide vs. placebo for the treatment of periodic paralysis Status: Completed Sponsor: University Rochester Funder: National Institutes of Health (NIH - USA) PI: Professor Michael Hanna Recruitment target: 40; Patients recruited: 14 Sansone VA, et al. Neurology 2016 Apr 12;86(15):1408-16. PMID: 26865514

The MRC Centre has been granted 'Orphan Medicinal Product' designation for diclofenamide for treatment of familial periodic paralysis by the European Commission

58. Phase II, multicentre, randomized, adaptive, double-blind, placebo controlled Study to assess Safety and Efficacy of Olesoxime (TRO19622) in 3-25 year old Spinal Muscular Atrophy (SMA) patients Status: Completed Sponsor: TROPHOS Funder: Association Française contre les Myopathies Newcastle PIs: Professor Hanns Lochmüller, Helen Roper Target: 10, Recruitment: 3 (pre-screening target achieved) London GOSH

11 | P a g e PI: Professor Francesco Muntoni, Recruitment target: 10 Recruitment target UK: 30 Results presented during the 66th American Academy of Neurology annual meeting (Philadelphia 2014). Trophos has been granted 'Orphan Medicinal Product' designation for olesoxime for the treatment of SMA by the European Commission and orphan drug designation by the US Food and Drug Administration.

59. The PATH Study Randomized, multicentre, double-blind, placebo-controlled, parallel-group phase III study to investigate the efficacy, safety and tolerability of 2 different doses of Igpro20 (subcutaneous immunoglobulin) for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) Status: Completed Sponsor: CSL Behring PI: Dr Michael Lunn Recruitment target: 5; Patients recruited 6

60. A Phase 2b Extension Study of PTC124 in Subjects with Nonsense-Mutation-Mediated Duchenne and Becker Muscular Dystrophy (Protocol Number -PTC124-GD-007e-DMD) Status: Completed Sponsor/Funder: PTC Therapeutics

61. A Phase 2a Study of Ataluren (PTC124) in Non-ambulatory Patients with Nonsense- Mutation-Mediated Duchenne/Becker Muscular Dystrophy (Protocol Number -PTC124-GD- 008-DMD) Status: Completed Sponsor: PTC Therapeutics Funder: PTC Therapeutics

62. A Phase 4 Prospective Exploratory Muscle Biopsy, Biomarker, and Imaging Assessment Study in Patients with Late-Onset Pompe Disease Treated with Alglucosidade Alfa – EMBASSY Sponsor: Genzyme Europe Funder: Genzyme Europe CI: Prof Volker Straub Target: 1, Recruited: 1

MRC Centre Natural History – Longitudinal Studies: Set-up Phase

63. Prospective. Longitudinal Study of the Natural History and functional status of patients with MyoTubular Myopathy (NatHis-MTM) Status: Set-up phase Sponsor: Institute of Myology PI: Professor Francesco Muntoni Recruitment target: 6-8

64. MYOPROSP: A prospective cohort study to identify a stratified approach in the diagnosis, treatment and delivery of care in adult idiopathic inflammatory myopathy Status: Set-up phase Planned start date: September 2016 Sponsor: University of Manchester Funder: MRC

12 | P a g e PI: Dr Pedro Machado Recruitment target: 31

65. LEMS Disease Registry – UK Proposal Status: Set-up phase Sponsor: BioMarin Europe Ltd PI: Professor Michael Hanna Patients target: 10 from the NHNN

66. Characterising electrophysiological patterns in neuromuscular disease over time using serial neurophysiology studies Status: Set up phase Sponsor: Newcastle upon Tyne Hospitals Foundation Trust CI/PI: Professor Hanns Lochmüller Recruitment Target: 63 participants

MRC Centre Natural History – Longitudinal Studies: Open Studies

STARTED POST JANUARY 2013

67. PhenoDM1: Myotonic Dystrophy type 1 (DM1) deep phenotyping to improve delivery of personalised medicine and assist in the planning, design and recruitment of clinical trials. Status: Open to recruitment Sponsor: Newcastle upon Tyne NHS Hospitals Foundation Trust Newcastle CI/PI: Professor Hanns Lochmüller Recruitment target: 200, patients recruited: 88 London NHNN PI: Dr Chris Turner Recruitment target: 200, patients recruited: 46

68. NIHR Pain Consortium (Bridge Neuropathic Pain) Status: Open to recruitment Funder: NIHR BioResource – Rare Diseases Sponsor: Cambridge University Hospitals NHS Foundation Trust & University of Cambridge London NHNN PI: Professor Mary M Reilly Patients recruited: 9 Newcastle PI: Professor Rita Horvath Patients recruited: 12

69. Becker Muscular Dystrophy - A Natural History Study to Predict Efficacy of Exon Skipping Status: Open to recruitment Sponsor: CINRG Newcastle CI/PI: Dr Michela Guglieri Recruitment target: 8; Patients recruited: 8

70. FSHD registry Status: Open to recruitment Funder: Muscular Dystrophy UK PI: Professor Hanns Lochmüller

13 | P a g e Patients recruited: 655

71. The International IBM Consortium Genetic Study Using Next Generation Sequencing to Unravel the Pathogenesis of Sporadic Inclusion Body Myositis (IBM) Status: Open to recruitment Funder: MRC UK recruiting target: 400 London NHNN CI: Professor Michael Hanna Patients recruited: 101 Newcastle PI: Dr Miller Patients recruited: 33 Gang Q, et al. Orphanet J Rare Dis. 2014 Jun 19; 9:88. PMID: 24948216. Gang Q, et al. Neurobiol Aging. 2015 Apr;36(4):1766.e1-3.PMID: 25670332

72. Hereditary Inclusion Body Myopathy-Patient Monitoring Program (HIBM-PMP): A Registry and Prospective Natural History Study to Assess HIBM Disease Status: Open to recruitment Sponsor: Ultragenyx Funder: Ultragenyx CI/PI: Professor Hanns Lochmüller Recruiting target: 25 ; Patients recruited: 25

73. Myotubular and Centronuclear Myopathy Patient Registry Status: Open to recruitment Funder: Myotubular Trust PI: Professor Hanns Lochmüller Patients recruited: 167

74. SMA REACH UK Spinal Muscular Atrophy Research and Clinical Hub UK Status: Open to recruitment Funder: UK SMA charity: SMA TRUST Sponsor: Great Ormond Street Hospital London GOSH CI: Professor Francesco Muntoni Recruitment target: 80; Patients recruited: 68 Newcastle PI: Professor Katie Bushby Recruitment target: 70; Patients recruited: 26 on hold awaiting extension

75. OPTIMISTIC Observational Prolonged Trial in Myotonic Dystrophy type 1 to Improve Quality of Life Standards, a Target Identification Collaboration Status: Ongoing but closed to recruitment Funder: EU Seventh Framework Programme Sponsor: The Newcastle upon Tyne Hospitals NHS Foundation Trust Newcastle CI/PI: Dr Grainne Gorman UK recruitment target: 72; Patients recruited: 64 (83 Participants)

76. Genotype-Phenotype in inherited neurodegenerative diseases Status: Open to recruitment

14 | P a g e Funder: Wellcome Trust Sponsor: Newcastle upon Tyne NHS Hospitals Foundation Trust PI: Professor Patrick Chinnery PI: Professor Rita Horvath Patients recruited: 451

77. CBYM338B2302: A Prospective Natural History Study in Sporadic Inclusion Body Myositis (sIBM) Status: Ongoing but closed to recruitment Sponsor: Novartis PI: Dr Pedro Machado/ Professor Michael Hanna Recruitment target: 30; Patients recruited: 37

78. Mito Exome Sequencing Study Status: Open to recruitment Sponsor: Guys and St Thomas Funder: Lily Foundation CI: Dr Charulata Deshpande Newcastle PI: Dr Robert McFarland Recruitment target: 25 families; Families recruited: 53 (158 participants) London PI: Professor Michael Hanna Recruitment target: 100 families; Families recruited: 17

79. Reproductive Decision Making in Mitochondrial Disease Status: Open to recruitment Sponsor: Newcastle Upon Tyne NHS Foundation Trust Funder: MRC Newcastle PI: Professor Doug Turnbull Recruiting target: 30; Patients recruited: 15

80. Factors Determining Disease Expression in Mitochondrial Disease Due to the m.3243 A>G Mutation Status: Open to recruitment Sponsor: NUTH Funder: BRC Confidence and Concept CI and PI: Dr Robert McFarland Recruitment target 16 (8 asymptomatic m.3243, 8 MELAS) Patients recruited: 0

81. International Guillain-Barre′ Syndrome (GBS) Outcome Study - IGOS Status: Open to recruitment Sponsor: Glasgow University Funder: Wellcome Trust/GBS Support group PI: Dr Michael Lunn Recruiting target: 10 from the NHNN, Patients recruited: 3 PI: Dr James Miller Target: 30, Current Recruitment: 27

STARTED PRE JANUARY 2013

82. Northstar

15 | P a g e Recording information on the management of your child with Duchenne muscular dystrophy in the UK North Star Clinical Network for Neuromuscular Disease Management Database Status: Open to recruitment Sponsor: UCL Funder: MDUK CI: Prof Francesco Muntoni PI: Adnan Manzur Recruitment at GOSH site: 245 PI: Dr Kate Bushby Recruitment at Newcastle site: 162

83. Identification of disease susceptibility genes associated with development and clinical characteristics of primary inflammatory muscle diseases, PM, DM and IBM Status: Open to recruitment Sponsor: University of Manchester Funder: University of Manchester/Myositis Support Group/Salford Royal NHS Foundation Trust PI: Professor Michael Hanna Recruited patients: 65 CI: Professor William Ollier PI: Dr James Miller Target: 100 in first year then approx. 20-30 per year. Total recruited to date: 143

84. CMT: A Natural History study Charcot-Marie-Tooth Disease and related disorders: A Natural History Study Status: Open to recruitment Sponsor: University College London Hospitals Funder: National Institutes of Health (NIH – USA) Recruitment target (UK):1000 London NHNN CI: Professor Mary M Reilly Patients recruited: 972 Newcastle PI: Dr Rita Horvath Patients recruited: 97

85. MRC Centre Mitochondrial Disease Patient Cohort: A Natural History Study and Patient Registry Status: Open to recruitment Sponsor: Newcastle Upon Tyne Hospitals NHS Foundation Funder: MRC CI: Dr R McFarland Total recruitment target 1500 Recruitment to date: 1327 Newcastle: 647 UCL: 363 Oxford: 138 Satellites: 179

86. The Natural History of Inclusion Body Myositis (IBM Net) Status: Open to recruitment Sponsor: University College Hospitals Funder: MDC PIs: Dr Matt Parton, Professor Michael Hanna Recruitment target 120-150; Patients recruited: 94 Cortese A, et al. Neuromuscul Disord. 2013 May; 23(5):404-12. PMID: 23489664

16 | P a g e 87. Kennedy’s Disease – Study and Register Status: Open to recruitment Sponsor: UCLH CI: Professor Michael Hanna Patients recruited: 86

88. Investigation of Human Neurological Ion Channel Disorders Status: Open to recruitment Sponsor: University College London Hospitals CI: Professor Michael Hanna Patients recruited: 122

89. AFM Natural History Study Outcome measures in Duchenne Muscular Dystrophy: A Natural History Study Status: Ongoing but closed to Recruitment Sponsor: UCL Institute of Child Health Funder: AFM London GOSH PI: Professor Francesco Muntoni Patients recruited: 16 Newcastle PI: Professor Volker Straub Patients recruited: 20

90. Biomarker Studies in MND/ALS Characterisation of a panel of disease biomarkers in peripheral blood from individuals with motor neuron disease Status: Ongoing but closed to recruitment Sponsor: Queen Mary University Funder: Motor Neurone Disease Association UCL PI: Dr Richard Orrell Patients recruited: 195 Lu CH, et al. Neurology. 2015 Jun 2;84(22):2247-57. PMID: 25934855

91. UK SMA registry Status: Open to recruitment Funder: SMA Support UK PI: Professor Hanns Lochmüller Patients recruited: 529

92. UK Myotonic Dystrophy patient registry Status: Open to recruitment Funder: Myotonic Dystrophy Support Group, Muscular Dystrophy UK PI: Professor Hanns Lochmüller Patients recruited: 624

93. Global FKRP registry Status: Open to recruitment Funder: LGMD2I Research Fund PI: Professor Volker Straub Patients recruited: 463

94. GNE myopathy-Disease Monitoring Programme (GNE-DMP): A registry and prospective observational natural history study to assess HIBM disease

17 | P a g e Status: Open to recruitment Funder: Ultragenyx and Newcastle University PI: Professor Hanns Lochmüller Patients recruited: 218

95. Jain Foundation Clinical outcome study of dysferlinopathy (limb-girdle muscular dystrophy type 2B) Status: Ongoing but closed to recruitment Sponsor: The Newcastle upon Tyne Hospitals NHS Foundation Trust Funder: Jain Foundation Newcastle CI/PI: Professor Kate Bushby Recruitment target: 20; Patients recruited: 43

MRC Centre Natural History – Longitudinal Studies: Completed Studies

STARTED POST JANUARY 2013

96. FSHD – NH Study A multicentre collaborative study on the clinical features, expression profiling, and quality of life of infantile onset facioscapulohumeral muscular dystrophy Status: Completed Sponsor: CINRG CI/PI: Dr Michela Guglieri Patients recruited: 9

97. A Prospective, Non-Interventional Clinical Assessment Study in X-Linked Myotubular Myopathy (XLMTM) Subjects Aged 3 Years and Younger Status: Open to recruitment Sponsor: Audentes Funder: Audentes PI: Prof Muntoni Recruitment target: 3

98. Study of clinical and radiological changes in teenagers with Duchenne muscular dystrophy theoretically treatable with exon 53 skipping (Pre-U7) Status: Completed Sponsor: Genethon Funder: Genethon London GOSH PI: Professor Francesco Muntoni Recruitment target: 5; Patients recruited: 5

99. Therapeutic trial of diaphragmatic pacing in MND/ALS (DiPALS) A randomised controlled trial in patients with respiratory muscle weakness due to motor neurone disease of the NeuRx RA/4 Diaphragm Pacing System Status: Completed Sponsor: Royal Free London NHS Foundation Trust Start date: March 2013 Funder: NIHR Health Technology Assessment Programme / Motor Neurone Disease Association / Department of Health subvention funding UCL PI: Dr Richard Orrell Recruiting target: 4; Patients recruited: 2 DiPALS Writing Committee, et al. Lancet Neurol. 2015 Sep;14(9):883-92. PMID: 26234554

18 | P a g e 100. A Study of Biological Prognostic Factors for IGM Paraproteinemic Anti-Mag Associated Peripheral Neuropathy Status: Completed Sponsor: UCL PI: Dr Michael Lunn Recruitment target: 45 patients

101. Natural History study of Hereditary Sensory Neuropathy type 1 secondary to SPTLC1 and SPTLC2 mutations Status: Completed Sponsor: University College London Hospitals PI: Professor Mary M Reilly Patients recruited: 35

STARTED PRE JANUARY 2013

102. Validation of prognostic biomarkers in Charcot-Marie-Tooth disease type 1A Status: completed Funder: AFM Sponsor: Newcastle upon Tyne NHS Hospitals Foundation Trust PI: Professor Rita Horvath Recruitment target: 20; patients recruited: 20

103. Prospective evaluation of gastrostomy in MND (PROGAS). Prospective evaluation of gastrostomy in MND (PROGAS). Status: Completed Sponsor: Royal Free London NHS Foundation Trust Start date: 2011 Funder: Motor Neuron Disease Association / South Yorkshire CLRN UCL PI: Dr Richard Orrell Recruiting target: 6; Patients recruited: 6 Stavroulakis T. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Mar;14(2):96-104. PMID: 22985431 ProGas Study Group. Lancet Neurology 2015, 14 (7): 702-709. PMID: 26027943

104. Incidence of complications of pregnancy in patients diagnosed with mitochondrial disease or carrying a mitochondrial DNA mutation Status: Completed Sponsor: Newcastle Upon Tyne NHS Foundation Trust Funder: MRC PI: Dr Robert McFarland UK Recruitment target: 200; Patients recruited: 151 (80 patients, 71 controls)

105. Non-Dystrophic Myotonias: Genotype and Phenotype correlation and longitudinal studies Status: Completed Sponsor: University College London Funder: National Institutes of Health (NIH – USA) PI: Professor Michael Hanna Patients recruited: 20 Trivedi JR. Brain. 2013 Jul; 136 (Pt 7):2189-200. PMID: 23771340

19 | P a g e 106. Andersen-Tawil Syndrome: Genotype and Phenotype correlation and longitudinal study Status: Completed Sponsor: University College London Funder: National Institutes of Health (NIH – USA) PI: Professor Michael Hanna Recruitment target >10; Patients recruited: 11

107. Episodic Ataxia Syndrome: Genotype-Phenotype correlation and longitudinal study Status: Completed Sponsor: University College London Funder: National Institutes of Health (NIH – USA) PI: Professor Michael Hanna Recruitment target >20; Patients recruited: 36 Graves TD. Brain 2014 Apr;137(Pt 4):1009-18. PMID: 24578548

108. Outcome measures in SMA type II and III Status: Completed Sponsor: UCL Institute of Child Health Funder: SMA Europe London GOSH PI: Professor Francesco Muntoni Newcastle PI: Professor Kate Bushby UK Recruitment target: 23; Patients recruited: 26

109. Peripheral Neuropathy outcome measures standardisation study (PERINOMS) Status: Completed Sponsor: Erasmus Medical Center PI: Dr Michael Lunn Recruitment target: 120; Patients recruited: 110

110. Standardized NBIA patient registry and natural history study Status: Completed Sponsor: University of Munich PI: Professor Patrick Chinnery Recruitment target: 20; Patients recruited: 24

111. Clinical Outcome Validation in non-ambulatory boys/men with DMD (Infants and children ages 1 month to 5 years) Status: Completed CI: Prof Kate Bushby (Newcastle) Target: 4, Recruited: 4.

112. SMA Europe Status: Completed Sponsor: University College London Hospitals NHS Funder: The SMA Trust CI: Prof Kate Bushby Target: 10, Recruited: 10.

MRC Centre Exercise Studies: Set-up Studies

113. Effect of orthoses and underfoot vibration on balance in neuropathy

20 | P a g e Status: Set-up phase Sponsor: St George's University of London Funder: St George's University of London Planned start date: September 2016 CI: Dr Gita Ramdharry Recruitment target: 10

114. BALTiC study: A feasibility analysis of home based BALance Training in people with Charcot-Marie-Tooth disease: Status: Set-up phase Sponsor: St George's University of London Funder: CMT United Kingdom Planned start date: September 2016 PI: Dr Gita Ramdharry Recruitment target: 16

115. An exploration of the 12 minute walk test and its impact on McArdle patients' confidence levels and pain descriptions: A mixed methods study Status: Set- up phase Sponsor: UCLH Funder: The National Brain Appeal, Small Acorns Fund and the Association for Glycogen Storage Disease (AGSD)-(UK). CI & PI: Dr. Ros Quinlivan Recruitment target: 21

MRC Centre Exercise Studies: Open Studies

STARTED POST JANUARY 2013

116. Exercise and Sarcopenia Status: Ongoing but closed to Recruitment Sponsor: Newcastle upon Tyne Hospitals NHS Foundation Trust Funder: MRC PI: Dr Grainne Gorman Collaborating site MRC Centre London (Recruitment at Newcastle only) Recruitment target: 36; Patients recruited: 34

117. Exercise, cognition and brain vitality Status: Open to recruitment Sponsor: Newcastle upon Tyne Hospitals NHS Foundation Trust Funder: MRC Newcastle PI: Dr Grainne Gorman Patients recruited: 29

118. Development a paediatric and adult home based assessment tool for monitoring symptoms of myasthenic syndromes. Status: Open to recruitment Sponsor: UCL / GOSH / UCLH Funder: MyAware Charity & UCL impact PI: Professor Francesco Muntoni Recruitment target: 120 (including adults and children); Patients recruited: 23 children & 49 adults.

MRC Centre Exercise Studies: Closed Studies

21 | P a g e STARTED POST JANUARY 2013

119. Exploring the causes of falls and balance impairments in people with neuromuscular diseases Status: Completed Sponsor: University College Hospitals Funder: NIHR PI: Dr Gita Ramdharry Recruiting target: 30; Patients recruited: 30 Hiscock A, et al.Physiotherapy. 2014 Mar;100(1):61-5. PMID:23954023

STARTED PRE JANUARY 2013

120. A study of physical activity comparing people with Charcot Marie Tooth disease to normal control subjects Status: Closed Sponsor: UCLH Funder: Muscular Dystrophy UK CI: Mary Reilly PI: Gita Ramdharry Recruitment: 20

121. Aerobic training in Charcot-Marie-Tooth disease and Inclusion Body Myositis. Status: Completed Sponsor: University College Hospitals PI: Dr Gita Ramdharry Recruiting target: 60; patients recruited: 47 Ramdharry, G. et al. Published online 16/08/16 http://dx.doi.org/10.1080/09638288.2016.1211180

122. Strengthening Hip muscles to improve walking distance in people with Charcot- Marie-Tooth disease Status: Completed Sponsor: University College London Hospitals Funder: Muscular Dystrophy UK PI: Professor Mary M Reilly Recruitment target: 32; Patients recruited: 32 Ramdharry GM, et al. J Peripher Nerv Syst. 2014 Dec;19(4):328-32. PMID: 25582960

123. Exercise training in patients with Mitochondrial disease: Assessing the benefits Status: Completed Sponsor: University Newcastle Funder: Muscular Dystrophy UK PI: Professor Doug Turnbull Collaboration site MRC Centre London (Hanna) Patients recruited: 9 Newcastle; 0 London

124. Cardiac adaptations to exercise in Mitochondrial disease Status: Completed Sponsor: Newcastle upon Tyne Hospitals NHS Foundation Trust Funder: MRC PI: Professor Doug Turnbull/Dr M Trenell Patients recruited: 39 Bates MG, et al. Int J Cardiol. 2013 Oct 9;168(4):3599-608. PMID: 23742928

22 | P a g e Galna B, et al. J Neurol. 2014 Jan;261(1):73-82. PMID: 24150688

MRC Centre Imaging Studies: Open Studies

STARTED POST JANUARY 2013

125. Brain imaging and cognition in patients with Duchenne muscular dystrophy Status: Open to recruitment Sponsor: Newcastle upon Tyne NHS Foundation Trust Funder: MDUK PI: Professor Volker Straub Recruitment target: 32 ; patients recruited: 11

126. Magnetic Resonance Imaging Characteristics of Inflammatory Neuropathies – a pilot study Status: Open to recruitment Sponsor: University College London Hospitals PI: Dr Michael Lunn Patients recruited: 20: 10 patient; 10 controls

127. Magnetic Resonance Imaging as an outcome measure in Motor Neuropathies: a pilot study Status: Open to recruitment Funder: BRC Sponsor: UCLH PI: Professor Michael Hanna Patients recruited: 40

128. A study of Qualitative Magnetic Resonance Imaging in Channelopathies Status: On hold Sponsor: UCL PI: Professor Michael Hanna Patients recruited: 0

STARTED PRE JANUARY 2013

129. A study using Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) in patients with Limb girdle muscular dystrophy 2I ; an assessment of skeletal and cardiac muscle damage Status: Open to recruitment Sponsor: Newcastle upon Tyne NHS Hospitals Foundation Trust Newcastle CI/PI: Professor Volker Straub Recruiting target (UK): 20, UNEW: ~10; Patients recruited: 9 London - Due to open shortly PI: Professor Michael Hanna Recruitment target: 6

MRC Centre Imaging Studies: Completed Studies

STARTED PRE JANUARY 2013

23 | P a g e 130. MRI in IBM and CMT A Study of Quantitative Magnetic Resonance Imaging and the Clinical Features of Inclusion Body Myositis and Charcot Marie Tooth Disease Status: Completed Sponsor: University College London Hospitals Funder: MRC PI: Professor T Yousry/Dr J Thornton Patients recruited: 72: 40 patients; 32 controls Morrow JM, et al. European Radiology 2014 Jul;24(7):1610-20.PMID: 24748539 Morrow JM, et al. Lancet Neurology 2016 Jan;15(1):65-77. PMID: 26549782

131. MRI in FKRP-Related LGMD2I A study using Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) in Patients with Limb Girdle Muscular Dystrophy 2I; an assessment of muscle damage Status: Completed Sponsor: Newcastle NHS Trust Funder: MRC PI: Professor Volker Straub Recruited patients: 22 Willis TA, et al. PLoS One. 2014 Feb 28;9(2):e90377. PMID: 24587344 Willis TA, et al. PLoS One. 2013 Aug 14;8(8):e70993. PMID: 23967145

132. A Study of Quantitative Magnetic Resonance Imaging to Monitor Disease Activity in Hypokalaemic Periodic Paralysis. Status: Completed Sponsor: UCL Funder: MRC PI: Professor Michael Hanna Recruitment: 24 (12 patients; 12 controls)

133. Evaluation and Optimisation of Muscle Imaging Biomarkers in Support of Non- ambulant Duchenne Muscular Dystrophy Studies Status: Completed Sponsor: UCL Institute of Child Health Funder: GSK PI: Professor Francesco Muntoni UK Patient target: 15; Patients recruited: 15 patients - 10 controls

24 | P a g e Core Activities

1. Stratified cohorts and Experimental medicine trials NCL Lead: Volker Straub (VS), UCL Lead: Mike Hanna (MH) One of the major successes of the MRC Centre has been the increased clinical trial activity across a large number of different neuromuscular diseases since the Centre launch. The MRC’s investment in establishing cohorts of patients with deeply phenotyped mitochondrial and neuromuscular diseases has facilitated natural history studies, aided clinical trial design and provided a mechanism to allow rapid recruitment of ‘trial ready’ patients to the extensive portfolio of clinical trials active at the MRC Centre for Neuromuscular Diseases. The steady increase in the number of trials is a reflection of the efforts to get ‘trial ready’ and of successful translational research activities and cohort building. All specialty groups within the MRC Centre have contributed to the increased clinical trial portfolio, which includes natural history studies with a focus on understanding disease progression and outcome measure development and interventional trials looking at exercise regimes, respiratory management, behavioural therapies and drug treatments. The interventional trials comprise phase I, phase II, phase III and phase IV studies, first in man and advanced therapies studies. Studies have been carried out in both paediatric and adult patient cohorts. For the vast majority of studies listed in the appendix on clinical trials Centre PIs are acting as chief investigators. The large number of commercial studies shows that pharmaceutical companies see the two MRC Centre sites as the most relevant centres of expertise nationally and in many cases internationally for trials in neuromuscular diseases.

Over the past 3 years the MRC Centre has successfully completed a large number of imaging, exercise, natural history and interventional trials, many of which were published in high impact journals (see reference list). More specifically we completed 41 studies in which the recruitment targets were met (5 imaging studies, 4 exercise studies, 12 longitudinal natural history studies and 20 interventional trials with a medicinal product). The Centre currently runs 66 open studies, including large multicentre cohort studies that include patient registries. The recruitment target for these studies is several thousand patients, many of which will be recruited by the two MRC Centre sites. Of the studies currently open across the two sites, we have 5 imaging studies, 5 exercise studies, 30 longitudinal natural history studies, and 26 interventional trials with a medicinal product. The recruitment for these studies is on target, which is a result of the excellent communication strategy of the centre, of the interaction with patient organisations and of the use of patient registries. The Mitocohort has proved a key resource for clinical and data analysis studies and since 2011, 36 study applications have been approved via the MRC Mitocohort steering committee to access data for research purposes. To date, over 2900 patient data sets have been successfully screened, of which over 1000 have been utilised for study purpose. 15 studies using the cohort are ongoing with 7 successful applications having been made this year alone. The cohort is utilized for both data analysis (20 projects approved) and screening for participation in clinical studies (16 studies approved, 355+ patients enrolled). The data has formed part of 5 PhD theses and has facilitated 18 publications since 2013 (see appendix 4), reflecting a range of collaborations between researchers in Newcastle, London and Oxford. Also, information from the analysis of cohort data has been instrumental in shaping and revising clinical care guidelines for mitochondrial disease patients, which are published on the Newcastle website. These Mitocohort derived guidelines are forming the basis of international mitochondrial disease management guidelines currently being formulated.

The added value of the MRC Centre for conducting both natural history studies and interventional clinical trials is the development of well characterized patient cohorts across the two Centre sites. The natural history studies are often a prerequisite for the start of interventional studies and have helped to gain expertise in the standardized assessment of patients across the sites. The mitochondrial cohort has recruited 1377 living participants through 3 major recruiting centres in Newcastle (691), London (366 UCL; 48 GOSH) and Oxford (106) with Newcastle coordinating the recruitment of a further 166 participants at secondary sites in the UK. A broad range of detailed

25 | P a g e clinical and genetic information is collated, providing a trial ready profile for each participant and a wealth of natural history data on mitochondrial disease. There are 19 different genotypes with at least 5 participants and much larger sub-cohorts of patients with m.3243A>G (370), large-scale single deletion of mtDNA (171), POLG1 (69) and m.8344A>G (61), making it possible to conduct appropriately powered studies of IMPs; one already in progress (Bezafibrate) and others at an application stage. Having worked together on the harmonisation of functional assessment scales like the North Star Ambulatory Assessment1,2 or the performance of Upper Limb3 module, sponsors for clinical trials appreciate that the MRC Centre sites provide helpful scientific advice for clinical trial design and deliver reliable data in clinical trials. The Centre has also been at the forefront of developing protocols for the quantitative assessment of muscle pathology using MRI and agreed standardized protocols for muscle imaging of the upper and lower limbs are implemented in London and Newcastle3,4,5,6,7,8,9,10

Translational research infrastructure established by the MRC Centre is used to both support and to benefit from clinical trial activity. The various patient registries that have been promoted by the MRC Centre are used for feasibility studies and for patient recruitment and the MRC biobank has helped to store valuable biomaterial from clinical trial patients for biomarker development11,12,13,14. The close collaboration of the MRC Centre with patient advocacy groups like Muscular Dystrophy UK, the SMA Trust or the Children's Mitochondrial Disease Network, have also helped to improve awareness for neuromuscular clinical trial activities and for recruitment into studies. Funding of clinical trial coordinators through the MRC Centre has transformed the way both London and Newcastle engage with pharmaceutical companies, academics sponsors, CROs, ethic committees, regulators and local R&D departments. The posts have played a fundamental role in extending the Centre’s clinical trial portfolio and in the increase in overall patient numbers enrolled in active studies.

The MRC Centre is currently setting up another 14 studies, including 2 exercise studies, 3 longitudinal natural history studies and 9 interventional clinical trials with a medicinal product. Several of these studies are looking at the application of advanced therapies in neuromuscular diseases, including stem cell and gene therapy. The planned stem cell trial is based on Giulio Cossu’s work on mesoangioblasts for the treatment of DMD patients. In the specific non- randomized, open label, phase I/IIa study, 5 non-ambulant DMD patients with mutations skippable for exon 51 will be injected with a single intra-muscular injection of mesoangioblasts engineered for exon 51 skipping.

Centre PIs have also worked together on new protocols and trial designs to start the first gene therapy studies in DMD and SMA in the UK. The planned DMD study, sponsored by Généthon, Évry, France, would use AAV8 to deliver a functional copy of a human microdystrophin gene in 10 patients in London (F. Muntoni) and Newcastle (V. Straub). The SMA gene therapy trial, sponsored by AveXis, Inc., US, is going to use AAV9 to deliver a functional copy of a human SMN1 gene and will also recruit patients in both London and Newcastle. The MRC Centre is now the first contact for many companies that are planning to do trials in neuromuscular diseases.

Recruitment Numbers: January 2013 November 2014 July 2016 Trials 507 772 1127 NH/Cohorts 2896 5423 7540

26 | P a g e Trials NH/Cohorts

Understanding the natural history of mitochondrial and neuromuscular diseases is critical to the design and conduct of clinical trials to treat these disorders. The Medical Research Council’s investment in establishing cohorts of patients with deeply phenotyped mitochondrial and neuromuscular diseases has facilitated natural history studies, aided clinical trial design and provided a mechanism to allow rapid recruitment of ‘trial ready’ patients to the extensive portfolio of clinical trials active at the MRC Neuromuscular Centre.

References 1NSAA; Ricotti V, et al., J Neurol Neurosurg Psychiatry. 2016 Feb;87(2):149-55 PMID: 25733532 2 De Sanctis R, et al., Neuromuscul Disord. 2015 Jan;25(1):14-8), PMID: 25454732 3 PUL; Mayhew A, et al., Dev Med Child Neurol. 2013 Nov;55(11):1038-45, PMID: 23902233 4 Morrow JM, et al., Lancet Neurol. 2016 Jan;15(1):65-77. PMID: 25649782 5 Morrow JM, et al., Neuromuscul Disord. 2013 Aug;23(8):637-46. PMID: 23810313 6 van der Ploeg A, et al., Mol Genet Metab. 2016 May 19. PMID: 27473031 7 Loughran T, et al., Radiology. 2015 May;275(2):570-8. PMID: 25575118 8 Willis TA, et al., PLoS One. 2014 Feb 28;9(2):e90377. PMID: 24587344 9 Hollingsworth KG, et al., Magn Reson Med. 2014 Dec;72(6):1610-9. PMID: 24347306 10 Willis TA, et al., PLoS One. 2013 Aug 14;8(8):e70993). PMID: 23967145 11 van den Bergen JC et al., J Neurol Neurosurg Psychiatry. 2015 Oct;86(10):1060-5. PMID: 25476005 12 Ayoglu B, et al., EMBO Mol Med. 2014 Jun 11;6(7):918-36. PMID: 24920607 13 Zaharieva IT, et al., PLoS One. 2013 Nov 25;8(11). PMID: 24282529 14 Anthony K, et al., JAMA Neurol. 2014 Jan;71(1):32-40. PMID: 24217213

2. Biobank UCL Lead: Francesco Muntoni (FM), NCL Lead: Hanns Lochmüller (HM) The MRC for Neuromuscular Diseases Biobank was established in 2008 as a unique resource of human plasma, serum, DNA, urine, muscle tissue and myoblast and fibroblast cell cultures from defined neuromuscular disorders. These materials are available to the basic science community for research purposes. Deliverables include: (i) Increasing sample size by continuing routine collection of myoblast and/or fibroblast cells from each patient undergoing diagnostics and extend sample collection to other UK centres. Target = 3000 (since the start of the biobank sample collection); (ii) Systematically collect biomaterials from each patient enrolled in clinical trials or natural history studies at the Centre or collaborating partners; (iii) Introducing immortalisation of targeted myoblast samples using recently developed method (retroviral transduction with both

27 | P a g e telomerase and cyclin-dependent kinase 4 expressing vectors) with French collaborators at the Institute of Myology; (iv) Introducing immortalisation of targeted fibroblast samples using the method previously used by NCL PIs (retroviral transfer of papillomavirus E6E7 genes); (v) Introducing MyoD-transfect human fibroblasts to generate myogenic cells for selected patients where muscle biopsies cannot be obtained; (vi) Collecting muscle derived stem cells; (vii) Introducing additional measures of quality control (ISO certification); (viii) Increasing collection of fibroblasts from neuropathy patients to be available for separate studies to generate iPS cells. The MRC Centre biobank has benefited a large number of basic, translational research and research & development projects within the Centre and generated high-profile publications.

Our established national MRC biobank of DNA, biological fluids, nerve, muscle and skin derived tissues, continues to grow and to be available to an increasing number of scientists nationally and internationally. The biobank continues to be a very successful pillar initiative of the MRC Centre, which underpins studies on gene discovery, on natural history, on biomarker assessment and novel biomarker developments, and on cell cultures availability for development of novel therapeutic strategies across a wide range of conditions of relevance for the MRC Centre. This resource has allowed also to support several new experimental grants. Moreover, the biobank is increasingly used for clinical trial and natural history samples, both for academic and commercially sponsored studies, and embedded in new national and international biobanking and data infrastructures such as BBMRI and RD-Connect. Cost recovery measures have been implemented, and increasing support by the host institutions, the BRCs and third party grants to ensure long-term sustainability of the biobank.

New noticeable achievements of the MRC Centre biobank since 2013 have been the recognition as an official member of Eurobiobank (with a regularly published catalogue of samples from the MRC biobank being made available in the Eurobiobank listing15. Following the recommendation of the SAB, we also created an iPS facility to exploit this new technology for supporting research in muscular dystrophies, neuropathies and in motorneuron diseases.

Regarding the overall sample number, the MRC biobank currently stores a total of 246 tissue, 3238 cell cultures; and 8311 other biological samples

Table 1. Updated list of samples stored in the MRC Biobank. Sample type stored* London Newcastle AC133+ 12 0 Muscle derived fibroblasts 7 0 Fibroblasts 806 843 Myoblasts 681 713 Sorted CD56+ myoblasts 3 0 Frozen muscle 239 0 Frozen skin 7 0 Immortalised fibroblasts 1 27 Immortalised myoblasts 13 20 Peripheral blood lymphocytes 30 0 PBMCs 16 0 Plasma 245 572 Serum 303 1733 PBLs-transformed 55 0 Pericytes 1 0 Synovial cells 10 0 Urine 74 731 DNA 126* 4046 RNA 0 481 Other 0 0

28 | P a g e TOTAL 2629 9166 *UCL has a separate established neurogenetic biobank for DNA where most of the UCL neuromuscular DNA samples are stored. Regarding the support for Gene discovery, the biobank has been instrumental in providing DNA, muscle tissue, and patients cell lines for the identification of novel genes to a number of independently funded initiatives (such as the Wellcome Trust funded 10KUK; the EU funded NeurOmics, coordinated by Lochmuller in Newcastle). Since 2013 the total number of new genes identified in which the MRC support has been acknowledged is (13 at UCL, 27 Newcastle), and the list of references can be found in the table below:

Novel genes

Zaharieva IT et al, Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy. Brain. 2016 Mar;139(Pt 3):674-91.

Scoto M et al. Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy. Neurology. 2015 Feb 17;84(7):668-79.

Rossor AM et al. Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain. 2015 Feb;138(Pt 2):293-310.

Cirak S et al. Isoprenoid synthase domain containing gene mutations are a common cause of congenital and limb girdle muscular dystrophies. Brain; 2013; 136:269-81.

Rudnik-Schöneborn S et al. Pontocerebellar hypoplasia type 1: Clinical spectrum and relevance of EXOSC3 mutations. Neurology. 2013 Jan 29;80(5):438-446.

Stevens E et al. Mutations in B3GALNT2 cause congenital muscular dystrophy with hypoglycosylation of alpha-dystroglycan. AJHG, 2013 Mar 7;92(3):354-65.

Oates EC et al. Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia. American Journal of Human Genetics 92, 1–9, June 6, 2013.

Carss KJ et al. Mutations in GDP-Mannose Pyrophosphorylase B Cause Congenital and Limb- Girdle Muscular Dystrophies Associated with Hypoglycosylation of alpha-Dystroglycan. Am J Hum Genet. 2013; 93(1):29-41.

Ravenscroft G et al. Mutations in KLHL40 Are a Frequent Cause of Severe Autosomal- Recessive Nemaline Myopathy. Am J Hum Genet. 2013 Jul 11;93(1):6-18.

Pitceathly RD et al. NDUFA4 Mutations Underlie Dysfunction of a Cytochrome C Oxidase Subunit Linked to Human Neurological Disease. Cell Rep. 2013 Jun 27;3(6):1795-805.

Yoshida-Moriguchi T et al.. SGK196 is a glycosylation-specific O-mannose kinase required for dystroglycan function. Science. 2013;341(6148):896-9.

Pitceathly RD et al. COX10 mutations resulting in complex multisystem mitochondrial disease that remains stable into adulthood. JAMA Neurol. 2013. Dec;70(12):1556-61

Gupta VA et al. Identification of KLHL41 Mutations Implicates BTB-Kelch-Mediated Ubiquitination as an Alternate Pathway to Myofibrillar Disruption in Nemaline Myopathy. Am J Hum Genet. 2013. 5;93(6):1108-17.

Logan CV et al. Loss of function mutations in MICU1 cause a novel disorder affecting brain and

29 | P a g e muscle and reveal primary alterations in mitochondrial Ca2+ signalling as a new disease mechanism. Nat Genet. 2014 Feb;46(2):188-93

Foley AR et al. Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain. 2014 Jan;137(Pt 1):44-56.

Scoto M et al Nebulin (NEB) mutations in a childhood onset distal myopathy with rods and cores uncovered by next generation sequencing. Eur J Hum Genet. 2013;21(11):1249-52.

Vissing J, et al. A heterozygous 21-bp deletion in CAPN3 causes dominantly inherited limb girdle muscular dystrophy. Brain. 2016 Aug;139(Pt 8):2154-63.

O'Connor E, et al. Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome. Brain. 2016 Aug;139(Pt 8):2143-53.

S Figueroa-Bonaparte et al. Mutational spectrum and phenotypic variability of VCP-related neurological disease in the UK. J Neurol Neurosurg Psychiatry. 2016 Jun;87(6):680-1.

T.A. Willis et al. Muscle hypertrophy as the presenting sign in a patient with a complete FHL1 deletion. Clin Genet 2016: 90: 166–170

Olsen RK, et al. Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency. Am J Hum Genet. 2016 Jun 2;98(6):1130-45.

Zurita Rendón O, et al. A Mutation in the Flavin Adenine Dinucleotide-Dependent Oxidoreductase FOXRED1 Results in Cell-Type-Specific Assembly Defects in Oxidative Phosphorylation Complexes I and II. Mol Cell Biol. 2016 Jul 29;36(16):2132-40.

Lewis-Smith D, et al. Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood. Neurol Genet. 2016 Mar 3;2(2):e59.

Scotton C, et al. Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy. J Cell Sci. 2016 Apr 15;129 (8):1671-84.

Boczonadi V, et al.Amyloid-β in mitochondrial disease: mutation in a human metallopeptidase links amyloidotic neurodegeneration with mitochondrial processing. EMBO Mol Med. 2016 Jan 25;8 (3):173-5.

Palmio J, et al. Novel mutations in DNAJB6 gene cause a very severe early-onset limb-girdle muscular dystrophy 1D disease. Neuromuscul Disord. 2015 Nov;25(11):835-42.

Köhler C, et al. Early-onset leukoencephalopathy due to a homozygous missense mutation in the DARS2 gene. Mol Cell Probes. 2015 Oct;29(5):319-22.

Belaya K, et al. Mutations in GMPPB cause congenital myasthenic syndrome and bridge myasthenic disorders with dystroglycanopathies. Brain. 2015 Sep;138(Pt 9):2493-504.

Bansagi B, et al. The p.Ser107Leu in BICD2 is a mutation 'hot spot' causing distal spinal muscular atrophy. Brain. 2015 Nov;138(Pt 11):e391. doi: 10.1093/brain/awv159. Epub 2015 Jun 10. PubMed PMID: 26063656; PubMed Central PMCID: PMC4620510

Pyle A, et al. Exome sequencing in undiagnosed inherited and sporadic ataxias. Brain. 2015 Feb;138(Pt 2):276-83.

30 | P a g e Marina Dusl et al. A 3′-UTR mutation creates a microRNA target site in the GFPT1 gene of patients with congenital myasthenic syndrome. Hum Mol Genet. 2015 Jun 15;24 (12):3418-26.

Michael Zech et al. Recessive Mutations in the α3 (VI) Collagen Gene COL6A3 Cause Early- Onset Isolated Dystonia. Am J Hum Genet. 2015 Jun 4;96 (6):883-93.

Sarkozy A et al. ANO5 gene analysis in a large cohort of patients with anoctaminopathy: confirmation of male prevalence and high occurrence of the common exon 5 gene mutation. Hum Mutat. 2013 Aug; 34 (8):1111-8.

Elizabeth Harris et al. Undiagnosed Genetic Muscle Disease in the North of England: an in Depth Phenotype Analysis. PLoS Curr. 2013 May 21;5.

Debbie Hicks et al. Mutations in the Collagen XII gene define a new form of extracellular matrix related myopathy. Hum Mol Genet. 2014 May 1;23 (9):2353-63.

Herrmann DN, et al. Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert- eaton myasthenic syndrome and nonprogressive motor neuropathy. Am J Hum Genet. 2014 Sep 4;95(3):332-9.

Balreira A, et al. ANO10 mutations cause ataxia and coenzyme Q deficiency. J Neurol. 2014 Nov;261(11):2192-8. ₁₀ Taylor RW, et al. Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies. JAMA. 2014 Jul 2;312(1):68-77.

Nicole S, et al. Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy. Brain. 2014 Sep;137(Pt 9):2429-43.

Pfeffer G, et al.Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. Brain. 2014 May;137(Pt 5):1323-36.

Chaouch A, et al. Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission. J Neuromuscul Dis. 2014;1(1):75-90.

Hicks D, et al. Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy. Hum Mol Genet. 2014 May 1;23(9):2353-63.

Foley AR, et al.Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain. 2014 Jan;137(Pt 1):44-56.

Pyle A, et al. Late-onset sacsinopathy diagnosed by exome sequencing and comparative genomic hybridization. J Neurogenet. 2013Dec;27(4):176-82.

Neeve VC, et al. Clinical and functional characterisation of the combined respiratory chain defect in two sisters due to autosomal recessive mutations in MTFMT. Mitochondrion. 2013 Nov;13(6):743-8.

Pfeffer G, et al. Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure. J Neurol Neurosurg Psychiatry. 2014 Mar;85(3):331-8.

Cossins J, et al. Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. Brain. 2013 Mar;136(Pt 3):944-56.

31 | P a g e Løseth S, et al.A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene. J Neurol. 2013 Jun;260(6):1504-10.

The MRC Biobank has also made available cultured cells from patients to further characterise the function of known genes:

Lopez RJ, et al. An RYR1 mutation associated with malignant hyperthermia is also associated with bleeding abnormalities. Sci Signal. 2016 Jul 5;9(435):ra68. Zhou H et al. RyR1 Deficiency in Congenital Myopathies Disrupts Excitation-Contraction Coupling.Hum Mutat. 2013;34:986-96.

Rokach O et al.. Establishment of a human skeletal muscle-derived cell line: biochemical, cellular and electrophysiological characterization. Biochem J. 2013 Oct 15;455(2):169-77.

Fernandez-Fuente M et al Adenovirus-mediated expression of myogenic differentiation factor 1 (MyoD) in equine and human dermal fibroblasts enables their conversion to caffeine-sensitive myotubes. Neuromuscul Disord. 2014 Mar;24(3):250-8. van der Ploeg A, er al. Prospective exploratory muscle biopsy, imaging, and functional assessment in patients with late-onset Pompe disease treated with alglucosidase alfa: The EMBASSY Study. Mol Genet Metab. 2016 May 19. pii:S1096-7192(16)30088-9.

Giunta M, et al. Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy. Hum Mol Genet. 2016 May 18. pii:ddw149.

Kullar PJ, et al Both mitochondrial DNA and mitonuclear gene mutations cause hearing loss through cochlear dysfunction. Brain. 2016 Jun;139(Pt 6):e33.

Guthrie G, et al. The neurological and ophthalmological manifestations of SPG4-related hereditary spastic paraplegia. J Neurol. 2016 Feb;263(2):419-20.

Meng J,et al. Autologous skeletal muscle derived cells expressing a novel functional dystrophin provide a potential therapy for Duchenne Muscular Dystrophy. Sci Rep. 2016 Jan 27;6:19750.

Vila MC,et al. Elusive sources of variability of dystrophin rescue by exon skipping. Skelet Muscle. 2015 Dec 1;5:44.

Braczynski AK, et al. Mittelbronn M. ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment. Biomed Res Int. 2015;2015:462592.

Chen Q, et al. Global N-linked Glycosylation is Not Significantly Impaired in Myoblasts in Congenital Myasthenic Syndromes Caused by Defective Glutamine-Fructose-6-Phosphate Transaminase 1 (GFPT1). Biomolecules. 2015 Oct 16;5(4):2758-81.

Horvath R, et al. SCP2 mutations and neurodegeneration with brain iron accumulation. Neurology. 2015 Nov 24;85(21):1909-11.

Blain A, et al. Absence of Cardiac Benefit with Early Combination ACE Inhibitor and Beta Blocker Treatment in mdx Mice. J Cardiovasc Transl Res. 2015 Apr;8(3):198-207.

Dusl M, et al. A 3'-UTR mutation creates a microRNA target site in the GFPT1 gene of patients with congenital myasthenic syndrome. Hum Mol Genet. 2015 Jun 15;24(12):3418-26.

32 | P a g e Euro L, et al. Structural modeling of tissue-specific mitochondrial alanyl-tRNA synthetase (AARS2) defects predicts differential effects on aminoacylation. Front Genet. 2015 Feb 6;6:21.

Müller JS, et al. How Abnormal RNA Metabolism Results in Childhood-Onset Neurological Diseases. J Neuromuscul Dis. 2015;2(Suppl 2):S31-S37. van den Bergen JC, et al. Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants. J Neurol Neurosurg Psychiatry. 2015 Oct;86(10):1060-5.

Blain AM, et al. Assessment of ventricular function in mouse models of muscular dystrophy: a comparison of MRI with conductance catheter. Neuromuscul Disord. 2015 Jan;25(1):24-31.

De Palma S, et al. Muscle proteomics reveals novel insights into the pathophysiological mechanisms of collagen VI myopathies. J Proteome Res. 2014 Nov 7;13(11):5022-30.

Boczonadi V, et al. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat Commun. 2014 Jul 3;5:4287.

Sitarz KS, et al. Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts. Mol Genet Metab. 2014 May;112(1):57-63.

Dick E, Kalra S, et al. Exon skipping and gene transfer restore dystrophin expression in hiPSC- cardiomyocytes harbouring DMD mutations. Stem Cells Dev. 2013 Jun 21.

Müller T, et al. Loss of dermatan sulfate epimerase (DSE) function results in musculocontractural Ehlers-Danlos syndrome. Hum Mol Genet. 2013 Sep 15;22(18):3761-72.

Zoltowska K, et al.Mutations in GFPT1 that underlie limb-girdle congenital myasthenic syndrome result in reduced cell-surface expression of muscle AChR. Hum Mol Genet. 2013 Jul 15;22(14):2905-13.

Marina AD, et al. NDUFS8-related Complex I Deficiency Extends Phenotype from "PEO Plus" to Leigh Syndrome. JIMD Rep. 2013;10:17-22.

Greally E, et al. Heterogeneous abnormalities of in-vivo left ventricular calcium influx and function in mouse models of muscular dystrophy cardiomyopathy. J Cardiovasc Magn Reson. 2013 Jan 16;15:4.

Biomarker discovery and natural history studies: The MRC biobank has been instrumental in the collection of serum, plasma and urine for the identification of novel biomarkers that could potentially be used to monitor disease progression and response to therapies (for example miRNAs in Duchenne muscular dystrophy and in spinal muscular atrophy, with cross validation in SMA mouse models following therapeutic intervention; and, in collaboration with industrial partner Pfizer, the identification of serum proteomics markers in DMD and the LGMD2B variant).

Heywood WE et al Global serum glycoform profiling for the investigation of dystroglycanopathies & Congenital Disorders of Glycosylation. Mol Genet Metab Rep. 2016 Apr 17;7:55-62.

Ferlini A et al, 204th ENMC International Workshop on Biomarkers in Duchenne Muscular Dystrophy 24-26 January 2014, Naarden, The Netherlands. Neuromuscul Disord. 2015 Feb;25(2):184-98

33 | P a g e Ayoglu B et al Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies. EMBO Mol Med. 2014 Jun 11;6(7):918-36.

Catapano F et al, Altered Levels of MicroRNA-9, -206, and -132 in Spinal Muscular Atrophy and Their Response to Antisense Oligonucleotide Therapy. Mol Ther Nucleic Acids. 2016 Jul 5;5(7):e331

Janghra N et al, Correlation of Utrophin Levels with the Dystrophin Protein Complex and Muscle Fibre Regeneration in Duchenne and Becker Muscular Dystrophy Muscle Biopsies. PLoS One. 2016 Mar 14;11(3):e0150818.

Scotton C, et al, Deep RNA profiling identified CLOCK and molecular clock genes as pathophysiological signatures in collagen VI myopathy. J Cell Sci. 2016 Apr 15;129(8):1671-84

Rokach O et al, Epigenetic changes as a common trigger of muscle weakness in congenital myopathies. Hum Mol Genet. 2015 Aug 15;24(16):4636-47.

Anthony K et al, Dystrophin quantification: Biological and translational research implications. Neurology. 2014 Nov 25;83(22):2062-9.

Mora M et al, The EuroBioBank Network: 10 years of hands-on experience of collaborative, transnational biobanking for rare diseases. Eur J Hum Genet. 2015 Sep;23(9):1116-23.

Stevens E et al. Flow Cytometry for the Analysis of a-Dystroglycan Glycosylation in Fibroblasts from Patients with Dystroglycanopathies. PLoS One. 2013 Jul 22;8(7):e68958.

De Palma S et al Muscle proteomics reveals novel insights into the pathophysiological mechanisms of collagen VI myopathies. J Proteome Res. 2014 7;13(11):5022-30.

Zaharieva IT et al. Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne Muscular dystrophy. PLoS One. 2013;8(11):e80263

Anthony K et al Biochemical Characterization of Patients With In-Frame or Out-of-Frame DMD Deletions Pertinent to Exon 44 or 45 Skipping. JAMA Neurol. 2014 Jan 1;71(1):32-40.

Anthony K et al Dystrophin quantification: biological and translational research implications Neurology, 2014;83:1–8

Oonk S, et al. Comparative mass spectrometric and immunoassay-based proteome analysis in serum of Duchenne muscular dystrophy patients. Proteomics Clin Appl. 2016 Mar;10(3):290-9.

Burch PM, et al. Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy. J Neuromuscul Dis. 2015 Sep 2;2(3):241- 255.

Coenen-Stass AM, et al. McClorey G, Manzano R, Betts CA, Blain A, Saleh AF, Gait MJ, Lochmüller H, Wood MJ, Roberts TC. Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics. Sci Rep. 2015 Nov 23;5:17014.

Pyle A, et al. Evaluation of exome sequencing variation in undiagnosed ataxias. Brain. 2015 Oct;138(Pt 10):e384.

Keogh MJ, et al. Clinical heterogeneity of primary familial brain calcification due to a novel

34 | P a g e mutation in PDGFB. Neurology. 2015 Apr 28;84(17):1818-20.

Ayoglu B, et al. Affinity proteomics within rare diseases: a BIO-NMD study for blood biomarkers of muscular dystrophies. EMBO Mol Med. 2014 Jun 11;6(7):918-36.

Cynthia Martin F, et al.Fibronectin is a serum biomarker for Duchenne muscular dystrophy. Proteomics Clin Appl. 2014 Apr;8(3-4):269-78.

Gavrilova R, et al. Fibroblast growth factor 21, a biomarker for mitochondrial muscle disease. Neurology. 2013 Nov 19;81(21):1808-9.

Moreover correlative studies between genomic markers and functional outcome measures have allowed researchers to confirm the role of previously identified gene modifiers in the course of DMD16.

In terms of support for translational research, the MRC biobank has been instrumental in providing cells for muscle stem cell research, focused on the characterisation of optimal stem cells for transplantation in muscular dystrophies, in development of viral gene therapy vector for autologous cell transplantation in muscular dystrophy; and the further characterisation of molecular pathway relevant for muscle stem cell function. Through collaborative work with C Denning and funded by MRC and BHF, iPS lines for DMD and myotonic dystrophy have been generated to derive disease and patient specific cardiac cell models. In addition cells from the MRC Centre has supported studies for target identification for splicing modification or allele selective silencing using antisense oligonucleotides for collagens 6 related muscular dystrophy; for RYR1 related myopathies; for SLPTC1 neuropathies and spinal muscular atrophy; for gene editing using CRSIPR/Cas9. In addition, both academic- and company-led clinical trial activity has been directly supported by the biobank (Optimistic, PhenoDM, AMO Pharma - tideglusib, FOR-DMD, COS dysferlinopathy).

Meng J et al. Autologous skeletal muscle derived cells expressing a novel functional dystrophin provide a potential therapy for Duchenne Muscular Dystrophy. Sci Rep. 2016 Jan 27;6:19750.

Wojtal D, et al. Spell Checking Nature: Versatility of CRISPR/Cas9 for Developing Treatments for Inherited Disorders. Am J Hum Genet. 2016 Jan 7;98(1):90-101

Meng J et al, The effect of the muscle environment on the regenerative capacity of human skeletal muscle stem cells. Skelet Muscle. 2015 Apr 28;5:11.

Di Foggia V et al, Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy. J Exp Med. 2014 Dec 15;211(13):2617- 33 Paco S et al.. Gene Expression Profiling Identifies Molecular Pathways Associated with Collagen VI Deficiency and Provides Novel Therapeutic Targets. PLoS One. 2013 Oct 11;8(10):e77430

Fletcher S et al. Antisense suppression of donor splice site mutations in the dystrophin gene transcript. Mol Genet Genomic Med. 2013 Sep;1(3):162-73.

Meng J et al. Human skeletal muscle-derived CD133(+) cells form functional satellite cells after intramuscular transplantation in immunodeficient host mice. Mol Ther. 2014 May;22(5):1008-17.

Whitmore C et al. The transgenic expression of LARGE exacerbates the muscle phenotype of dystroglycanopathy mice. Hum Mol Genet. 2014 Apr 1;23(7):1842-55.

Jonuschies J et al. The Human Desmin Promoter Drives Robust Gene Expression for Skeletal Muscle Stem Cell-Mediated Gene Therapy. Curr Gene Ther. 2014 14(4):276-88.

35 | P a g e Di Foggia V et al. Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy. J Exp Med. 2014 Dec 15;211(13):2617- 33.

Nightingale H, et al. Emerging therapies for mitochondrial disorders. Brain. 2016 Jun;139(Pt 6):1633-48.

Rodríguez Cruz PM, et al. Clinical features of the myasthenic syndrome arising from mutations in GMPPB. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):802-9.

Wilson IJ, et al. Mitochondrial DNA sequence characteristics modulate the size of the genetic bottleneck. Hum Mol Genet. 2016 Mar1;25(5):1031-41.

Burki U, et al. Development and Application of an Ultrasensitive Hybridization-Based ELISA Method for the Determination of Peptide-Conjugated Phosphorodiamidate Morpholino Oligonucleotides. Nucleic Acid Ther. 2015 Oct;25(5):275-84.

Payne BA, et al. Clinical and pathological features of mitochondrial DNA deletion disease following antiretroviral treatment. JAMA Neurol. 2015 May;72(5):603-5.

Barresi R, et al. Conserved expression of truncated telethonin in a patient with limb-girdle muscular dystrophy 2G. Neuromuscul Disord. 2015 Apr;25(4):349-52.

Boczonadi V, et al. Investigating the role of the physiological isoform switch of cytochrome c oxidase subunits in reversible mitochondrial disease. Int J Biochem Cell Biol. 2015 Jun;63:32-40.

Cottenie E, et al. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2. Am J Hum Genet. 2014 Nov 6;95(5):590-601.

Gorman GS, et al. . Clonal expansion of secondary mitochondrial DNA deletions associated with spinocerebellar ataxia type 28. JAMA Neurol. 2015 Jan;72(1):106-11.

Griffin HR, et al. Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations. Genet Med. 2014 Dec;16(12):962-71.

Greer KL, et al. Targeted exon skipping to correct exon duplications in the dystrophin gene. Mol Ther Nucleic Acids. 2014 Mar 18;3:e155.

Willis TA, et al. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross-sectional study. PLoS One. 2014 Feb 28;9(2):e90377.

Zou Y, et al. Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice. Hum Mol Genet. 2014 May 1;23(9):2339-52.

Spendiff S, et al. Mitochondrial DNA deletions in muscle satellite cells: implications for therapies. Hum Mol Genet. 2013 Dec 1;22(23):4739-47.

Dick E, et al. Exon skipping and gene transfer restore dystrophin expression in human induced pluripotent stem cells-cardiomyocytes harboring DMD mutations. Stem Cells Dev. 2013 Oct 15;22(20):2714-24.

Pfeffer G, et al. New treatments for mitochondrial disease-no time to drop our standards. Nat Rev Neurol. 2013 Aug;9(8):474-81.

36 | P a g e Boczonadi V, et al. Altered 2-thiouridylation impairs mitochondrial translation in reversible infantile respiratory chain deficiency. Hum Mol Genet. 2013 Nov 15;22(22):4602-15.

Lorenzoni PJ, et al. Salbutamol therapy in congenital myasthenic syndrome due to DOK7 mutation. J Neurol Sci. 2013 Aug 15;331(1-2):155-7.

Klymiuk N, et al. Dystrophin-deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle. Hum Mol Genet. 2013 Nov 1;22(21):4368-82.

Rutschow D, et al. S151A δ-sarcoglycan mutation causes a mild phenotype of cardiomyopathy in mice. Eur J Hum Genet. 2014 Jan;22(1):119-25.

Vissing J, et al. Diagnosis of Pompe disease: muscle biopsy vs blood-based assays. JAMA Neurol. 2013 Jul;70(7):923-7.

Blain A, et al. Beta-blockers, left and right ventricular function, and in-vivo calcium influx in muscular dystrophy cardiomyopathy. PLoS One. 2013;8(2):e57260.

Establishment of human induced Pluripotent Stem Cells (iPSCs) – derived skeletal muscles as a model system to phenocopy muscular dysfunction: Fibroblasts lines obtained from patients’ biopsies carrying the most common mitochondrial mutations were subjected to non-integrating Sendai virus mediated reprogramming. Established stable iPSCs lines were validated for positive expression of pluripotency factors and formation of three germ layers: mesoderm, endoderm and neuroectoderm. Validated cell lines were subsequently karyotyped to exclude lines with chromosomal rearrangements. Validated human iPSCs has been successfully differentiated into multinucleated skeletal muscles via stepwise differentiation protocol. The differentiation culture system contains defined myogenic factors, which allow to recapitulate developmental stages of myogenesis. Each stage of differentiation including: late presomatic mesoderm specification, myoblast formation, cell cycle withdrawal, commitment and cell fusion to form multinucleated myotubes is assessed via quantification of differentiation markers at the RNA and protein level. Assessed skeletal muscles markers include: Brachyury, Cdx2, Msgn1, Pax3, Pax7, MyoD, MyoG, MyHC, Desmin. Population of proliferative cells is assessed by Ki67 protein, which is present in actively cycling cells. Maturation is performed by reducing knock-out serum replacement or supplementing media with selected serum components. Current working progress focusses on the transferring the monolayer culture conditions into scaffold-facilitated 3D culture. This part of the project is done in collaboration with UCL Eastman Dental institute specializing in materials and tissue engineering. Muscles are one of the most affected tissues by mitochondrial disorders. The onset of neuromuscular disorders is typically in adulthood, and affected subjects can present with general muscle weakness, dysphagia, and spino-cerebellar signs with impaired gait coordination, dysmetria, and dysarthria. Established model system is applied to mechanisms of observed pathology. Currently used methods include bioenergetics, electrophysiology and . We have just started a project funded by EBiSC (https://www.ebisc.org/about- ebisc/the-project.php) aiming to generate and use quality-controlled, disease-relevant research grade iPSC lines as models of neuromuscular diseases.

Samples distribution: More than 687 research projects based at UCL, NCL and internationally have benefited from the samples supplied by the Biobanks (below) supporting research into neuromuscular and other disorders. To date, the research has been published in 44 articles acknowledging the contribution of the MRC Centre biobanks.

37 | P a g e Independently funded projects supported by the MRC Biobank:

UCL 2013-2017 Horizon 2020. Neuromics. €300.000 (to UCL). Muntoni UK PI 2013-2016 Improving standards of care and translational research in SMA. SMA Trust £264,000. Muntoni PI 2013-2016. NIHR Rare Disease Initiative: Neuromuscular Diseases: Deep Duchenne muscular dystrophy phenotyping. NIHR. £ 355,000. Muntoni PI 2014-2106 Cure CMD. Serum miRNA in dystroglycanopathies. $25,000. Muntoni PI 2014-2017 Peptide Conjugated oligonucleotides for splice switching therapy of SMA. MRC. £1,008,000. Wood PI, Muntoni Co-PI 2014-2017 A multicentre natural history study on DMD. AFM € 852,000. Muntoni Coordinator and CI 2014-2016 Allele-selective suppression by antisense oligonucleotide as a therapeutic strategy for collagen VI-related congenital muscular dystrophy. MDC. £115,861. Muntoni PI 2015-2017 Identification of microRNAs as biomarkers and potential therapeutic targets in spinal muscular atrophy. SMA Europe 108,000€. Muntoni PI 2015-2017 Vascular abnormalities in Spinal Muscular Atrophy. £99,500. GOSH Charity, Muntoni PI 2015-2017 Repair of duplications in dystrophin using CRSIPR/ Cas9. Muscular Dystrophy UK. £118,4000. Muntoni PI 2016-2017 Horizon2020. EPIBSC. An European Bank for induced pluripotent Stem Cells. £300,000 to UCL, Muntoni PI

Newcastle 2012-2017 European Commission, 7th framework programme, Integrated Project, “Neuromics”, Co-Investigator, principal investigator O Riess (Tübingen University, Germany), Newcastle award value £850,000 2012-2016 European Commission, 7th framework programme, Integrated Project, “Optimistic”, Co-Investigator, principal investigator B van Engelen (Nijmegen University, The Netherlands), Newcastle award value £319,609 2015-2016 Association Francaise contre les Myopothies (AFM) – “Validation of serum biomarkers for DMD”, £21,230 2015-2017 National Institute for Health Research (NIHR) – “PhenoDM1 Myotonic Dystrophy type 1 (DM1) deep phenotyping to improve delivery of personalised medicine”, £192,000 2015-2018 British Heart Foundation – “Deep molecular phenotyping of myotonic dystrophy (DM1)”, £72,413 2016-2021 Wellcome Trust – “Exploring novel molecular targets and disease mechanisms in mitochondrial protein synthesis deficiencies to develop novel treatments in mitochondrial disease”, principal investigator R Horvath, £1,152,904.00 2016-2019 Medical Research Council (MRC) – “Exosomal Protein Deficiencies: How Abnormal RNA Metabolism Results in Childhood-Onset Neurological Diseases”, principal investigator R Horvath, £558,443.25 2016-2017 Medical Research Council (MRC) – “New genomics approaches to explore the neurogenetic disease burden of consanguineous marriages in Turkey”, principal investigator H Lochmüller, £253,515.00

References 15 Mora M et al. The EuroBioBank Network: 10 years of hands-on experience of collaborative, transnational biobanking for rare diseases. Eur J Hum Genet. 2015 Sep;23(9):1116-23 PMID: 25537360

38 | P a g e 16 van den Bergen JC et al, Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants. J Neurol Neurosurg Psychiatry. 2015 Oct;86(10):1060-5. PMID: 25476005

3. MRI UCL Leads: Tarek Yousry (TY) and John Thornton (JT), NCL Lead: Andrew Blamire (AB) We aim to deploy MRC Centre-established MRI protocols in patient experimental medicine studies and continue technical development to fully exploit MRI to provide non-invasive, objective and responsive readouts. Imaging studies led by PIs within the MRC Centre cover three research areas – clinical studies, preclinical studies and basic methodology development.

Clinical - Natural History Studies We are leading a number of natural history studies across the five MRC Centre disease themes using MRI to evaluate muscle degeneration. Data from these studies is an essential first step in establishing MRI as an outcome measure for interventional trials.

IBM and CMT1A (Hanna, Yousry, Reilly, Thornton) We have completed baseline, and 1, 2 and 3 year follow up in MRC Centre for Neuromuscular Diseases prospective MRI IBM and CMT1A cohort study, with participation of 20 IBM and 20 CMT patients, and 29 controls. We have published reproducibility and normative control data17 and demonstrated that lower-limb fat-fraction is a responsive outcome measure correlating with muscle strength and clinical scales18; analysis of year 2&3 data is ongoing. To demonstrate multi-centre viability we implemented our London MRC Centre MRI protocol at a collaborating cite in the US (University of Iowa, PI Shy), and completed baseline and 1 year scans in a of CMT1A patient cohort; these data will be cross-analysed with that from our London CMT1A cohort. We have acquired MRI for a Novartis-sponsored sporadic IBM natural history study, baseline data demonstrating MRI readout and patient-reported outcome-based functional grading correlation. Amyotrophic Lateral Sclerosis and Kennedy’s Disease (Greensmith, Hanna, Thornton, Yousry) Funded in part by an UCLH NIHR Biomedical Research Centre t grant (£251,259; 2014-2017), a longitudinal study characterising skeletal muscle MRI in closely-phenotyped cohorts with amyotrophic lateral sclerosis (n=24) and Kennedy’s disease (n=12) and controls (n=20) is underway. Baseline measurements are complete and follow-up measurements up to 1yr are ongoing. Hereditary Sensory Neuropathy (Reilly, Thornton) In anticipation of a pending clinical trial to assess L-serine efficacy in this patient population, we have completed a longitudinal natural history study in a cohort of 34 Hereditary Sensory Neuropathy Type 1 patients demonstrating that MRI-obtained muscle fat-fraction, in contrast to conventional clinical/functional measures, provides a responsive outcome measure in this group of patients varying extensively in their clinical presentation. LGMD2I - (Hollingsworth, Straub, Murphy, Thornton, Morrow, Carlier, Stojkovic, Vissing) The LGMD2I study is a 5 year follow-up imaging investigation of a patient cohort originally investigated in 2009/201019,20, with the aim to further identify the rate of muscle involvement and quantify disease progression. The study is collecting our standardised quantitative lower limb imaging protocol in 32 of the original patients across 4 centres (Newcastle, UCL, Institute de Myologie in Paris and Copenhagen). Data collection is complete in Newcastle and Copenhagen and is pending in London and Paris. Patients in Newcastle have also undergone a quantitative MR cardiac function examination. PhenoDM1- myotonic dystrophy type 1 (DM1) deep phenotyping to improve delivery of personalised medicine and assist in the planning design and recruitment of clinical trials (Lochmuller, Turner, Hanna) The PhenoDM1 study commenced in April 2015 with funding from the NIHR Rare Diseases Translational Research Collaboration and is a wide-ranging patient characterisation study

39 | P a g e including our standardised muscle MRI protocol. The study will scan 25 patients in Newcastle and 25 patients in London. BIOIMAGE-NMD – (Blamire, Straub, Clark, Muntoni) The BIOIMAGE-NMD study (FP7, led from Newcastle) has a broad remit around developing and evaluating new imaging approaches as outcome measures for trials in NMD. BIOIMAGE-NMD is collecting natural history muscle MR data in patients across the consortium (Newcastle, London, Paris, Leiden, Leuven, Rome) and also through links to the AFM funded study Outcome measures in Duchenne Muscular Dystrophy with a total of at least 36 patients being scanned. Non-ambulant Duchenne Muscular Dystrophy (Muntoni, Yousry, Hanna, Thornton) In GSK-sponsored investigation acquisitions are complete for an upper-limb MRI natural history study in non-ambulant DMD boys. Forearm measurements at baseline, 6 and 12 month follow up (15 patients and 10 matched controls) show robust progressive fat-fraction increase, before significant change in functional measures (presented at WMS 2014; manuscript under review). Clinical Outcome Study in Dysferlinopathy (Bushby, Straub, Blamire, Hollingsworth) The JAIN foundation funded clinical outcome study in dysferlinopathy is led by MRC Centre PIs, with the MRI investigation being a major arm of the study which is jointly coordinated from Newcastle (Blamire, Straub) and Paris. Newcastle are also the central image processing and analysis site to extract whole body muscle involvement, muscle fat fraction and water T2 (inflammation) in lower limbs. The international cohort of nearly 200 patients is being studied annually with the longest-enrolled patients now approaching the end of year 3. The imaging data has highlighted the rate of disease progression and identifies key muscles as putative trial outcome measures depending on patient age and disease activity. Hypokalaemic periodic paralysis (Hanna, Reilly, Thornton, Yousry) We have completed a study of quantitative magnetic resonance imaging to monitor disease activity in 12 hypokalaemic periodic paralysis patients and matched controls (Symposium Neuoradiologica; Istanbul 2014), identifying an age-dependent therapeutic window21.

Clinical - Interventional Studies using Exon Skipping MRC Centre PIs are leading 3 FP7 funded programmes with major imaging components being evaluated as outcome measures for response to exon skipping interventions in Duchenne muscular dystrophy; SKIP-NMD (Muntoni) using a PMO compound to skip exon 53, SCOPE- DMD using an AON compound to skip exon 45 and BIOIMAGE-NMD using an AON compound to skip exon 53 (and others). The nature of these trials ties delivery of the imaging studies to the commercial direction of the SME partners which has impacted particularly on both SCOPE-DMD and BIOIMAGE-NMD where our partner Biomarin ended clinical trials and eventually withdrew from the NMD treatment space in May 2016. Imaging in AON treated patients has been collected in a small number of patients in the UK (skipping exon 53), with the BIOIMAGE study also funding the MRI scans and receiving imaging data from the Biomarin study of Drisapersen (skipping exon 51, US sites only). While the clinical trials are now ended valuable data on outcome assessment by MRI is now being evaluated.

Preclinical & Translational Studies A number of imaging studies are underway in preclinical systems in Newcastle to better understand genotype-phenotype relationships in transgenic models and to create enhanced imaging techniques. BIOIMAGE-NMD is developing diffusion MRI techniques (Newcastle) and data analysis approaches (UCL) tailored for the imaging properties and microenvironment of the muscle. Ageing and disease-related changes in muscle have been observed between mdx and wild-type mice and demonstrate diffusion sensitivity to changes in muscle fibre permeability. Using advanced data modelling to evaluate a broad range of possible imaging protocols a muscle optimised muscle diffusion imaging method has been defined. The diffusion imaging protocol has been translated from the preclinical to clinical 3T scanners and a multi-site reproducibility study in healthy volunteers is underway (Newcastle, London, Paris, Leiden). The Newcastle team within BIOIMAGE-NMD has also achieved 18F labelling of AON compounds with high yield for positron emission tomography (PET) imaging. AON efficacy in the mdx model is unchanged by the labelling scheme and studies combining 18F-PET with MRI are being

40 | P a g e developed with a view to measure real-time AON bio-distribution and to determine whether the muscle fibre permeability data from diffusion MRI relates to AON uptake by PET. It is widely recognised that there are neurological deficits in patients with DMD and work in Newcastle is evaluating brain morphology in the mdx mouse. Work by our MRC Centre student (Emine Bagdatlioglu) has conducted longitudinal preclinical neuroimaging studies comparing wild-type, mdx and Cmah- mice. Differences in brain size, ventricular volume, MR tissue properties and blood-brain-barrier permeability are evident between models and over time with ageing. Current work is relating these morphometric brain data against the behavioural and histological data.

Methodology Development Accelerated imaging Our work applying quantitative MRI to measure muscle fat-fraction has proven this approach as the most sensitive imaging endpoint in trials to judge the longitudinal effects of pharmaceutical, dietary or exercise interventions. However, the MRI acquisition is conventionally slow, placing a burden on study participants (especially children and the elderly) and requiring substantial financial resources. We have pioneered the development of accelerated MRI in the IMPRESS (Imaging using Compressed Sensing) project (PI Kieren Hollingsworth, Medical Research Council 2012-2015, £370k), substantially reducing acquisition times using compressed sensing methods for muscle fat fraction measurements and cardiac function assessments in neuromuscular diseases (such as Duchenne muscular dystrophy). A validation study of skeletal muscle fat fraction in Becker muscular dystrophy has demonstrated that the acquisition time of 3D fat fraction imaging can be reduced by up to a factor of 5 (a reduction of scan time from 4 minutes 23 seconds to 55 seconds). Two independent observers registered no loss of image quality at factor 5. We have demonstrated how to optimise the reconstruction, and that these reconstructions significantly outperform acceleration by today’s gold standard technique, parallel imaging22,23,24 . Muscle T2 Quantification We hypothesise that muscle-water T2, obtained independently of muscle fat fraction will provide a marker of early-stage disease. The IDEAL-CPMG method for simultaneous fat-water T2 quantification, originally developed at our Centre in collaboration with GSK, and recently further developed (Sinclair 2016) has been deployed in a number of natural history studies within the MRC Centre (IBM and CMT1A, Hereditary Sensory Neuropathy, Hypokalaemic Periodic Paralysis) and beyond25. In an alternative approach, in an EPSRC CASE industrial-collaboration PhD studentship (MRC Centre PI Thornton) with GSK, we are developing optimised numerical fitting methods to extract muscle-water T2 from conventional multi-echo acquisitions. Sodium imaging In Newcastle (Blamire, Straub) we have begun to evaluate the role of sodium imaging in muscle. Scan protocols have been established on our preclinical MRI scanner to acquire images of total sodium and to separate intra- from extra-cellular sodium based on T1 differences and preliminary data has been collected in wild-type mice. We anticipate using these methods in studies of sodium-proton exchange inhibitors. An MRC Centre Infrastructure grant (Hanna) has enabled us to develop a compatible multi-nuclear MR platform across the MRC Centre sites (Newcastle, UCL Institute of Neurology, and UCL Institute of Child Health) to facilitate cross-centre translation of sodium and other non-proton methods, and full participation in future multi-centre studies requiring these modalities. Protocol Standardization Standardisation and validation of imaging methods and protocols across both MRC Centre sites and link with NMD centres across Europe & USA remains a core centre activity, exemplified by the participation in the MYO-MRI eCOST Action BM1304, "Applications of MR imaging and spectroscopy techniques in neuromuscular disease: collaboration on outcome measures and pattern recognition for diagnostics and therapy development", (Proposer Volker Straub), to fund European collaboration which specifically aims to improve diagnosis and understanding of muscle pathology; Develop multicentric imaging outcome measures; explore new contrasts,

41 | P a g e targets and imaging techniques for NMD and explore strategies for muscle imaging texture analysis.

Funding All of the above studies are funded by both by the MRC Centre and other grants obtained by the MRI group in the MRC Centre (see appendix 3).

References 17 Morrow JM et al. Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers. Eur Radiol. 2014 Jul;24(7):1610-20. PMID: 24748539 18 Morrow JM et al. MRI biomarker assessment of neuromuscular disease progression: a prospective observational cohort study. Lancet Neurol. 2016 Jan;15(1):65-77. PMID: 26549782 19 Willis TA et al. Quantitative muscle MRI as an assessment tool for monitoring disease progression in LGMD2I: a multicentre longitudinal study. PLoS One. 2013. Aug 14;8(8):e70993. PMID: 23967145 20 Willis TA et al. Quantitative magnetic resonance imaging in limb-girdle muscular dystrophy 2I: a multinational cross-sectional study. PLoS One. 2014. Feb 28;9(2):e90377. PMID: 24587344. 21 Morrow JM et al. Reproducibility, and age, body-weight and gender dependency of candidate skeletal muscle MRI outcome measures in healthy volunteers. Eur Radiol. 2014 Jul;24(7):1610-20. PMID: 24748539 22 Loughran T et al. Improving highly accelerated fat fraction measurements for clinical trials in muscular dystrophy: origin and quantitative effect of R2* changes. Radiology. 2015 May;275(2):570- 8. PMID: 25575118 23 Hollingsworth KG et al. Investigating the quantitative fidelity of prospectively undersampled chemical shift imaging in muscular dystrophy with compressed sensing and parallel imaging reconstruction. Magn Reson Med. 2014 Dec;72(6):1610-9. PMID: 24347306 24 Hollingsworth KG. Reducing acquisition time in clinical MRI by data undersampling and compressed sensing reconstruction. Phys Med Biol. 2015 Nov 7;60(21):R297-322. PMID: 26448064 25 Mankodi A et al. Quantifying disease activity in fatty-infiltrated skeletal muscle by IDEAL-CPMG in Duchenne muscular dystrophy. Neuromuscul Disord. 2016 Jul 28. PMID: 27593185

4. Animal Models UCL Lead: Linda Greensmith (LG), NCL Lead: Volker Straub (VS) Although the MRC Centre does not have funding to directly support animal research, animal models continue to be of importance to the Centre and several Centre PIs have significant programmes of research that involve NMD animal models. We have strong links with MRC Harwell (EF, LG), and several PIs are members of the MRC Mouse Network (DT, FM, EF, LG, MR, MK, MH). The MRC Centre enables human clinical scientists with human cohorts to link with animal scientists working with animal models to work projects towards translation, for example by informing animal model preclinical therapy assessment. The MRC Centre has a four-fold strategy to add value, support and inform existing MRC investments in NMD animal model research. i). A series of translational PhD projects in the Centre which utilise preclinical animal models in each of the major disease themes A number of animal models of neuromuscular disorders are currently being investigated by MRC Centre PIs and have been utilised by several of the Centre PhD students. Some examples of the current animal models of NMD under study by Centre PIs include: Inclusion Body Myositis (IBM): We have now established colonies of two lines of mice expressing human VCP mutations that model Inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD), and hereditary inclusion body myopathy. Dr Mhoriam Ahmed in LG’s lab is leading on this project along with MRC Student Charlotte Spicer.

42 | P a g e Muscle Channelopathies: Analysis of mice with mutations in SCN4A by Centre PIs MH, MK and LG, in collaboration with MRC Harwell have shown that AMPK plays a role in myotonia and periodic paralysis. This study involved Centre PhD student Phil McGoldrick and Postdoc Roope Männikkö. Motor Nerve Disorders and Inherited Neuropathies: Distal Hereditary Motor Neuropathy (dHMN): a homozygous splice mutation in the HSJ1 gene (DNAJB2) which decreases the expression of the 2 main isoforms HSJ1a and HSJ1b has been identified as a novel rare variant of dHMN. This mutation causes a loss-of-function of HSJ1 and is linked to a pure lower motor neuron disease. This study has been undertaken in LG’s lab with MRC Students Alex Rossor and Anna Gray. Charcot-Marie-Tooth disease type 1A (CMT type1A): using the C3 mouse model of CMT type1A, Centre PIs (KJ, MK) have shown that Schwann cell c-Jun is elevated in nerves of C3 mice. This elevation of c-Jun in the Schwann cells of C3 nerves serves to prevent loss of myelinated sensory axons, particularly in distal nerves, suggesting that Schwann cells have two contrasting functions in CMT type 1A: on the one hand they are the genetic source of the disease, on the other, they respond to it by mounting a c-Jun-dependent response that significantly reduces its impact. Spinal Bulbar Muscular Atrophy (SBMA): We continue to work with the AR100 mouse model of SBMA (Kennedy’s Disease) in which we have undertaken a preclinical trial of Arimoclomol (Malik et al, 2013). More recently we have established a new colony of mice that model a more aggressive form of SBMA and which express 121 CAG repeats (AR121 mice). This work has been undertaken in LG’s lab with MRC Centre students Anna Gray and Helen Devine. Motor Neuron Disorders (MND): Centre PIs (EF, LG) use a number of models of MND, including the most widely used and best characterised mutant SOD1 mouse model. These groups have also been collaborating with MRC Harwell to identify and characterise mice with endogenous point mutations in the new ALS-causing genes TDP-43 and FUS. This work has been undertaken as part of a large collaborative project in the EF and LG labs with their co- supervised MRC Student Phil McGoldrick. Centre PIs have also been studying transgenic mice that over express the molecular chaperone HSJ1. Overexpression of HSJ1 is capable of protecting motor neurons in the mutant SOD1 mouse model of ALS. Centre PhD student Anna Gray in LG’s lab contributed to this study. The Centre has very recently established a colony of mice with mutations in the Senataxin gene (SETX). SETX mutations are known to be causative for a form of juvenile onset ALS (ALS4) and have also been shown to be a rare cause of hereditary motor neuropathy. Characterisation of these mice will be undertaken in LG’s lab with MRC Student Helen Devine. Duchenne Muscular Dystrophy (DMD): Centre PIs (JEM, FM) use the mouse model for DMD (the mdx mouse) to investigate the mechanisms of muscle fibre death and whether this can be prevented (lead by postdoctoral research associate Dr Maximilien Bencze; in collaboration with LG). Immunodeficient mdx mice (mdx nude) are used in stem cell transplantation studies. Work on stem cells of human origin that have been lentivirally transduced to express dystrophin has been done in collaboration with Hanns Lochmuller, Adrian Thrasher and Olivier Danos. PhD student Bruno Doreste is working on factors within irradiated host muscle that enhance donor mouse satellite cell engraftment. Spinal Muscular Atrophy (SMA): In SMA transgenic mice, the Smn gene is knocked out and the human SMN2 gene is introduced. Mice that carry at least one copy of endogenous Smn gene show no phenotype; Mice that have no Smn gene but two copies of human SMN2 gene (Smn +/-; (SMN2)2+/-) show severe phenotypes similar to type I SMA patients and a very short lifespan about 10 days; Mice that carry no copy of Smn gene but four copies of human SMN2 gene (Smn +/-; (SMN2)2+/+) show mild phenotypes with only tail and ears necrosis and a normal life expectancy. Studies led by Centre postdoc Dr Haiyan Zhou in FM’s laboratory include: investigation of the molecular pathogenesis of SMA, evaluation of potentially therapeutic strategies (e.g. antisense oligonucleotide therapy and small molecules) and motor functional studies of neurodegeneration and response to therapeutic intervention (in collaboration with LG). ii) MRC Centre PIs play an active role in optimising the success of the MRC Neuromouse Consortium and have strong links with MRC Harwell

43 | P a g e We collaborate closely with the one of the world’s major mouse genetics establishments, the MRC Mammalian Genetics Unit, Harwell, in the development and analysis of new models of disease. Recently, this has involved the NEUROMOUSE CONSORTIUM, which was set up by Professor Elizabeth Fisher, a member of the MRC Centre for Neuromuscular Disease, and is co- run with Professor Doug Turnbull, Dimitri Kullmann, Francesco Muntoni and others. The Neuromouse Consortium aims to help disperse mouse models relevant to human disease to the neuro-behavioural community in the UK, and also to provide experts in human and mouse neurological and psychiatric disease who can give essential insight and advice to Harwell on phenotyping platforms for the analysis of mouse models, and on genes for the prioritisation of specific mutants. While current efforts have focussed on models related to motor neuron disease, Harwell has been advised by Professor Dimitri Kullmann on electrophysiology and related platforms and has been making efforts to generate a new model for Professor Muntoni. iii) Centre PI’s and PhD students continue to utilise the successful MRC Centre NMD animal phenotyping laboratory at UCL established using the original Centre award allocation (50k) This facility is used on a regular basis by LG and EF’s laboratory in the phenotyping of all of their NMD mouse models, and by MRC Centre Students and postdocs. iv) We participate in regular meetings on neuromuscular animal models. The MRC Mouse Network continues to organise regular meetings to update members on lines produced, phenotyping tests being performed, and any phenotyping results of interest to date. MRC Harwell also continues to offer regular training courses to which MRC Centre staff and students are invited. These include the following recent courses: i) Bioinformatics of Mutant Mouse Resources: designed to give participants an understanding of high-throughput phenotype data, enabling them to interpret this data, compare it against other phenotype sources and identify mouse models of relevance to their clinical domain of interest. ii) Understanding and Using the Light Microscope, intended for those new to light microscopy, with practical sessions and expert advice on how to operate both basic microscopes and advanced research instruments. iii) Mouse Embryo and Spermatozoa Cryopreservation training course, covering the techniques needed to store and use frozen sperm and embryos, and a robust method of IVF. The overarching aim of our animal model strategy, linked to other supported programmes, is to understand how reversible functional impairment turns into irreversible structural deficits and how experimental therapy can prevent, delay or compensate this. We have studied this in three key areas: (i) Abnormalities of axonal transport: have emerged as a key factor in several NMDs. Centre PIs have examined axonal transport in vivo e.g. in mouse models of MND (Loa and mSOD1 mice) and in vitro in models of motor neuropathies (HSPB1, loa) and CMT1A (C3). (ii) How do neuromuscular channelopathies cause muscle degeneration? We have examined mouse models of muscle channelopathies (periodic paralysis) with mutations of Na (SCN4A) and calcium (CACNA1S) channels and RyRs. (iii) Mouse therapy studies: a) Protein Aggregation/IBM: using the mutant VCP mouse model of IBMPFTD, LG’s lab has examined the effects of manipulation of muscle cell protein homeostasis including heat shock protein and proteosomal regulation. The results indicate that long term treatment with Arimoclomol significantly ameliorates the histopathological features of IBM in muscle, resulting in improved muscle strength – study undertaken by MRC Centre Postdoc Mhoriam Ahmed with Centre PhD student Charlotte Spicer. b) Ion Channel Disease: we have developed translational neurophysiological biomarkers of nerve excitability profiling for application in rodents, non-human primates and human volunteers and patients for drug discovery studies. Using the mutant SOD1 mouse model of ALS, Centre PIs (HB and LG) have developed a theoretical model of mouse motor nerve excitability, and validated it by application to recordings from mouse axons with membrane potential altered by polarizing currents using multiple excitability tests. Multiple excitability measures of nerves in mutant SOD1 mice before and during disease progression indicated a modest membrane depolarization in SOD1(G93A) axons at symptom onset, possibly due to deficient energy supply. However,

44 | P a g e previously described excitability changes in ALS patients, suggesting altered sodium and potassium conductances, were not seen in the mice. This suggests that those changes relate to features of the human disease that are not well represented in this animal model. c) Muscular Dystrophy: we are examining a) the optimal type of donor muscle stem cells for systemic delivery and are using lentiviral vectors to transduce these cells with the largest possible dystrophin construct (opti-dystrophin); b) undertaking a proof of principle study of autologous stem cells lentivirally-transduced to express opti-dystrophin; c) using cardiac MRI to monitor natural history and effects of therapy on cardiac function in the Mdx mouse. Funding and publications All of the above studies are funded by a variety of grants obtained by the groups using animal models in the MRC Centre (see appendix 3) and have resulted in the publications outlined in appendix 4.

5. MRC Centre PhD and Education Programme (see appendix 6).

45 | P a g e Performance against milestones 2013-2018

Metric Baseline Target Current How Outputs Measured Qualitative Outcomes 2013 2018 status 2016 Resource generation 1 Numbers of samples biobanked and 1800 3000 11,795 Six monthly reporting of metrics and publication in annual High impact publications based on work utilising biobank samples distributed report

2 Numbers of patients enrolled in NMD 2000 3000 9527 Six monthly reporting of metrics and publication in annual Patient availability for studies, greater patient cohorts report engagement

3 Validated MR clinical endpoints for 8 16 9 Numbers of patients enrolled in MR studies of clinical Publications, SOPs for MR evaluation, adoption as trial trials outcomes annually outcomes

4 Numbers of students enrolled in MRC 9 18 27 Annual returns, time to PhD completion Availability of highly trained cohort of scientists training programme

5 Attendees annually at MRC 200 210 210 Numbers of participants, participant feedback, web hits Greater engagement of NMD clinical and academic conference on podcasts community

6 Numbers of additional centres 0 2 21 Numbers of samples and patients reported six monthly and Greater engagement of NMD clinicians, patients contributing to biobanks, annual report cohorts, trials 7 New high level science 4 6 6 Numbers of new staff attracted to MRC Centre Greater critical mass recruitment to MRC Centre

8 Number of industry 5 10 38 Numbers of industry contacts and contracts Greater industry involvement in NMD partnerships

Know how 9 Number of experimental 16 20 21 Numbers of orphan drugs associated to centres, trials initiated Proof of principle studies completed, high impact medicine studies initiated publications

10 Number of new genes identified and 6 24 41 Numbers of new disease genes collected annually Publications, new disease targets for therapies classified

11 New targets for antisense 1 2 3 Numbers of experimental antisense studies annually Grants, publications, new clinical studies therapy in NMD

12 Initiation of a clinical study for stem 0 1 0 Milestones to clinical study including safety, preclinical Proof of principle clinical study, grants, publications cell therapy in NMD evaluation

13 Numbers of experimental 1 4 4 Numbers of patients enrolled in exercise studies Understanding the role of exercise in disease and therapy exercise studies initiated annually

14 Overallscientific/academicoutput 138 200 311 Numbers of joint papers and value of grants including MRC, Increased high impact publications and grant awards More thanonePI (449 total EU 2008-present) Total PINMDoutput 563 600 810 (1373 total 2008-present)