MRC Strategic Award to establish an International Centre for Genomic Medicine in Neuromuscular Diseases

Neuromuscular Diseases (NMD) affect at least 17 million children and adults globally. They cause either premature death or are chronic diseases causing lifelong disability with economic impact. They include many different disorders affecting muscle and nerve function and account for ~20% of all non-infectious neurological diseases. Examples include muscular dystrophies, congenital myopathies, neuropathies, motor neuron diseases, muscle channelopathies and mitochondrial diseases. Advances in genetics have improved our ability to diagnose patients in the UK, and this has resulted in improved patient care and enabled clinical trials. However the benefits of genetic advances have not been realised in Official Development Assistance (ODA) defined Lower and Middle Income Countries (LMICs), partly because of a lack of neurologists trained specifically in genomic NMD medicine. NMDs are commonly genetic and are inherited. Identifying genetic pathways and applying genetic testing has led to some of the most important advances in disease understanding alongside patient management plans and the development of new therapies. Many of the key interventions involve the inexpensive practical applications of widely available medical technology (e.g. low-cost off-licence medication, targeted vaccination, cardiac monitoring and respiratory care), but their application is contingent on making a precise diagnosis. For example, a precise genetic diagnosis can lead to a personalised and often simple management plan following established care guidelines that includes basic screening for known complications (e.g. cardiac, respiratory, gastroenterological and metabolic) and often simple interventions that improve health outcomes - interventions that could be implemented easily in LMICs providing an accurate genetic diagnosis is made. In the UK, a muscle biopsy has been the mainstay in the investigation algorithm in many patients, but this requires a specialist laboratory equipped for frozen section analysis with a growing panel of diagnostic antibodies. However, recent advances in genomics provide the opportunity to diagnose with high precision based on a DNA sample and clinical data collected remotely. Our central objective is to build ethnically diverse cohorts of children and adults with NMDs and undertake genomic analysis to find known and identify new disease genes. We will increase the number of patients with a precise genetic diagnosis to both improve patient care and to increase knowledge on the comparative genetic architecture of NMDs across four continents. This is a brand new transcontinental programme led by UK professors at UCL, Newcastle and Cambridge Universities. The research programme will train a new generation of academic doctors, generate the world's largest cohort of 15,000 ethnically diverse NMD patients and will investigate the causative genes. We will work with five LMIC clinical and academic centres in: India, Turkey, South Africa, Zambia and Brazil. The trained doctors will be the future clinical academic leaders to undertake research and improve NMD patient care in these countries. The fellows will already be fully trained in neurology and will spend a year in the UK for specialist training in NMD genomic medicine and spend three years in their country building NMD patient cohorts that will be assessed in detail clinically and will undergo full genetic analysis to achieve a precise diagnosis and optimise patient management. All data produced will be anonymised and shared by all researchers. Importantly, we have access to several thousand ethnically matched control DNAs already and will build this control resource further, complementing those available through the Genomics England 100,000 genomes project, the NIHR BioResource and international collaborative resources. We will train a new generation of NMD doctors who will pursue their research career in their own country, discover new genes and improve patient care.