MICA: MRC Centre for Neuromuscular Diseases

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Neuromuscular diseases (NMD) are an important group of disabling conditions affecting about 150,000 children and adults in the UK. They are caused by impairment of peripheral nerve and/or skeletal muscle function. Patients with these diseases develop muscle weakness and the severity can range from death in childhood or early adult life through to life long disability & dependence. Many patients also have heart and breathing muscle weakness which can add to disability and sometimes be fatal. These NMD conditions are commonly genetic and may run in families. They can also be acquired-for example through antibody attack as in "autoimmune" NMD or due to premature degeneration of muscle. Genetic examples include muscular dystrophy (~1 in 3500), Charcot Marie Tooth (CMT) neuropathy (~1 in 2500) and mitochondrial diseases (~1 in 5000). Acquired examples include chronic nerve inflammation (~1 in 1500) and a muscle degeneration/inflammation condition called inclusion body myositis (~1 in 10,000). It is clear that NMD represent an important unmet health burden for the nation. However, relative to other neurological diseases such as epilepsy and multiple sclerosis, NMD have received less attention by government and other UK funding bodies. This is despite the excellent clinical infrastructure provided by several large clinical neuromuscular centres and the nationally commissioned NHS funding for care and diagnosis of some NMD lead by MRC Centre PI's (eg congenital muscular dystrophy, channelopathies and mitochondrial diseases). Furthermore, there has been significant progress in NMD discovery science, frequently lead by internationally high profile UK clinicians and scientists, but translation of this scientific discovery into clear benefit for UK patients has been disappointing so far.We set up this MRC Centre to develop ways to bridge this "translational gap" between scientific discovery and patient benefit. We identified six main reasons (obstacles) why scientific discoveries were not clearly benefiting patients. We developed specific core activities to overcome each obstacle. Most notably we found there was a lack of UK trials culture for these conditions. That means that there were not many trials happening, doctors treating patients did not think there was much that could be done, and patients were not being given the opportunity to get involved in the research & trials that were happening. By setting up key core activites, in just four years, we have shifted the situation towards a trial and experimental medicine culture in the UK. Key activities we developed & which are now valuable UK available resources:1. Stratified cohorts: collections of patients eligible for entry into trials and research2. Experimental trials support: a system of coordination and support to enable testing of new therapies in patients3. Neuromuscular human cell biobank: collecting muscle cells from patients to test new therapies4. MRI biomarker studies: using MRI scans to accurately measure muscles and assess if experimental treatments are working5. Training programmes to train more young scientists to undertake trials and develop new therapies6. Getting clinicians & animal scientists working closely together to work out which are the best cell & animal models on which to test new therapiesThese core activities & our clinician scientist networks have resulted in a ten-fold increase in clinical trials & an even larger increase in patients entered into research cohorts. We now want to build on this success to embed a trials culture in UK practice.In the UK there is no other centre that focuses on systematically linking discovery research to experimental medicine for NMD. This MRC Centre has lead the UK efforts in the last four years. The mission of a renewed MRC Centre is to achieve impact by translating science into experimental medicine & find treatments for adults & children with disabling/fatal neuromuscular diseases.