Appendix 1. MRC Centre Principal Investigators 2016 Director Professor Michael Hanna Co-directors London 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 genetics 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 Wellcome Trust 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