Eighth UK Neuromuscular Translational Research Conference 19th – 20th March 2015 Centre for Life Times Square Newcastle upon Tyne Table of Contents Welcome from the MRC Centre for Neuromuscular Diseases and from Muscular Dystrophy UK ........................................................................................................ 2 About the MRC Centre for Neuromuscular Diseases and Muscular Dystrophy UK ......................... 6 Patient organisations ........................................................................................................... 9 Programme ....................................................................................................................... 10 Poster List ........................................................................................................................ 15 Invited Speaker Abstracts ................................................................................................... 23 Poster and Platform presentation abstracts ........................................................................... 29 Clinical trials in the MRC Centre for Neuromuscular Diseases ................................................. 107 Delegate list .................................................................................................................... 154 MRC Centre for Neuromuscular Diseases staff list................................................................. 160 Conference planning group ................................................................................................ 162 Sponsors ........................................................................................................................ 164 1 Welcome to the eighth annual meeting of the MRC Centre for Translational Research in Neuromuscular Diseases UK Neuromuscular Translational Research Conference Newcastle 2015 Dear Colleagues, We are delighted to welcome you to Newcastle for the eighth annual UK Neuromuscular Translational Research Conference. We are very pleased that this conference continues to be jointly hosted by the MRC Centre for Neuromuscular Diseases and Muscular Dystrophy UK. In addition, this year we have worked closely with colleagues in the London-Newcastle MRC Centre steering committee, the MRC Mitochondrial Biology Unit in Cambridge, the Wellcome Trust Centre for Mitochondrial Research in Newcastle and the MRC Functional Genomics Unit in Oxford to develop the scientific translational research programme. Major translational themes this year include mitochondrial disease, genomic data and its use in support of translational research for neuromuscular diseases, the identification and validation of new targets in neuromuscular diseases and the increasing role of MRI biomarkers for diagnosis and disease/therapy monitoring. We are delighted to welcome a world-leading neuromuscular clinician scientist who will deliver the conference named lecture; Professor Carsten Bonnemann, Senior Investigator and Chief of the Neuromuscular and Neurogenetic Disorders of Childhood section, NIH, USA, will give the third John Walton Lecture (dedicated this year to the memory of David Gardner- Medwin). The mission of the MRC Centre is to translate science into new experimental medicine trials and find treatments for children and adults with serious muscle wasting diseases. Collaborative working and interdisciplinarity represent a fundamental platform for successful translation. The MRC Centre works to bring together clinicians, scientists, patient organisations and patients in order to advance the UK translational research effort. This is a particularly exciting time in the field as scientific discoveries are revealing an increasing number of tractable therapeutic targets. The MRC Centre continues to work closely with all its partners to support the development of a clinical trials culture and aims to embed an experimental clinical trials network in neuromuscular clinical practice. We will continue to work hard to form effective research and clinical links with as many other UK neuromuscular groups as possible. In the renewed Centre (renewed 2013-2018) we have developed strong experimental medicine links with, and received important coordinated support from, three NHS NIHR Biomedical Research Centres based at University College London Hospitals, Great Ormond Street and at Newcastle University Hospitals. The MRC Centre is also pleased to contribute to the NIHR National Rare Diseases Translational Research Collaboration. The MRC Centre was established in 2008 as a joint partnership between the UCL Institute of Neurology, Queen Square, the UCL Institute of Child Health and Newcastle University and was renewed for a further five years in 2013. The Centre continues to be closely linked to its partner NHS organisations, University College London Hospitals NHS Foundation Trust, Great Ormond Street Hospital for Children NHS Foundation Trust and Newcastle upon Tyne Hospitals NHS Foundation Trust. The Centre has also developed strong links with groups in Oxford and Cambridge which we will develop further in this current phase of the Centre. 2 Over the next two days this conference aims to showcase a wide range of high quality scientific neuromuscular research from many UK groups, international colleagues and industry partners. We have received over 120 high quality abstracts, and there will be platform presentations and dedicated poster sessions each day as well as guided poster discussions. This year we have also introduced for the first time a poster flash session where abstracts are selected to be presented in 5 minute slots using only three slides. We hope this will prove a popular session. There will be five £500 poster prizes for young investigators. Accepted abstracts will be published in a special supplement of the journal Neuromuscular Disorders with Professor Mary M. Reilly as the special guest editor. This year we were have also introduced a patient day which takes place the day before the conference. As the Centre Director, I would very much like to thank Professor Mary M. Reilly who has lead the joint MRC-Muscular Dystrophy UK meeting scientific planning team: Professors Kate Bushby, Doug Turnbull, Francesco Muntoni, Dame Kay E. Davies, and Dr Marita Pohlschmidt. I also sincerely thank Christine Oldfield and Marita Pohlschmidt for their very hard work in organizing this meeting. I am very grateful for the interest, sponsorship and support of industry colleagues who are working with us to develop new therapies for patients with neuromuscular diseases. Once again this annual meeting has been oversubscribed. We are very encouraged that there continues to be such strong interest in neuromuscular translational research from throughout the UK and beyond. We sincerely hope that you have a stimulating, productive and entertaining two days in Newcastle. Professor Michael G. Hanna Professor Mary M. Reilly Director Co-Director MRC Centre for Neuromuscular MRC Centre for Neuromuscular Diseases Diseases, UCL Institute of Child Health UCL Institute of Neurology Professor Francesco Muntoni Professor Katie Bushby Co-Director, ICH/GOS Co-Director, Newcastle MRC Centre for Neuromuscular MRC Centre for Neuromuscular Diseases, Diseases Newcastle University UCL Institute of Neurology 3 Professor Doug Turnbull Professor Dame Kay E Davies Co-Director Director, MRC Functional Genomics Unit MRC Centre for Neuromuscular University of Oxford Diseases Newcastle University Dr Marita Pohlschmidt Director of Research, Muscular Dystrophy UK 4 Welcome from Robert Meadowcroft – Chief Executive of Muscular Dystrophy UK I am writing on behalf of Muscular Dystrophy UK to extend a very warm welcome to the 2015 UK Neuromuscular Translational Research Conference organised in partnership between the MRC Centre for Neuromuscular Diseases and Muscular Dystrophy UK (formerly known as the Muscular Dystrophy Campaign). Muscular Dystrophy UK has supported this important meeting since its inception and we are delighted that scientists and clinical researchers from across the field of neuromuscular disorders have this opportunity to come together to showcase progress in the field. Indeed, many advances have been made through research into neuromuscular disorders backed by the charity’s research funding over more than 50 years. During this time our families and supporters have raised more than £55 million to fund cutting-edge science and research, whilst a further £50 million of the charity’s funds has been invested in care and support for families. I am pleased to say our research programme is expanding and we are now working in partnership with a number of national and international charities to continue funding high quality research. As more genes are identified and a patient’s genetic diagnosis is more precise, families today often decide to restrict their donations to research in a specific condition and the charity has established new mechanisms to support them. Last year saw the first international call made by the charity for research into a single condition, Ullrich congenital muscular dystrophy, and we are very pleased this new partnership involves four leading charities from France, Ireland, Switzerland and the USA. We are encouraged by the growing number of clinical trials taking place and delighted that potential treatments are now on the horizon for a number of conditions. Translarna, the first drug for Duchenne muscular dystrophy addressing the underlying genetic cause has received regulatory approval from