MICA: MRC Centre for Neuromuscular Diseases

MICA：MRC 神经肌肉疾病中心

• 批准号: MR/K000608/1
• 负责人: Michael Hanna
• 金额: $ 402.79万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK000608%2F1
• 关键词: MICA; MRC; Centre; Neuromuscular; Diseases

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.

神经肌肉疾病(NMD)是一组重要的致残性疾病，在英国约有15万儿童和成年人受到影响。它们是由周围神经和/或骨骼肌功能受损引起的。患有这些疾病的患者会出现肌肉无力，严重程度可从童年或成年早期死亡到终生残疾和依赖。许多患者还患有心脏和呼吸肌无力，这可能会增加残疾，有时甚至是致命的。这些NMD疾病通常是遗传性的，可能在家族中发生。它们也可以获得--例如，通过抗体攻击，如“自身免疫性”NMD，或由于肌肉过早退化。遗传学的例子包括肌营养不良(3500例中约1例)、夏科马里牙(CMT)神经病(2500例中约1例)和线粒体疾病(5000例中约1例)。后天的例子包括慢性神经炎(1500例中约1例)和一种称为包涵体肌炎的肌肉变性/炎症情况(10,000例中约1例)。很明显，NMD对国家来说是一个重要的未得到满足的健康负担。然而，相对于癫痫和多发性硬化症等其他神经系统疾病，NMD受到政府和其他英国资助机构的关注较少。尽管几个大型临床神经肌肉中心提供了优秀的临床基础设施，而且国家委托NHS为MRC中心PI领导的一些NMD的护理和诊断提供资金(例如先天性肌营养不良、通道病变和线粒体疾病)，但仍是如此。此外，NMD发现科学取得了重大进展，经常由国际知名的英国临床医生和科学家领导，但到目前为止，将这一科学发现转化为对英国患者的明确好处一直令人失望。我们成立了这个MRC中心，以开发方法来弥合科学发现和患者利益之间的“转换鸿沟”。我们找出了科学发现没有明显惠及患者的六个主要原因(障碍)。我们制定了具体的核心活动来克服每一个障碍。最值得注意的是，我们发现英国缺乏针对这些情况的试验文化。这意味着没有太多的试验正在进行，治疗病人的医生认为没有太多可以做的事情，病人也没有机会参与正在进行的研究和试验。通过建立关键的核心活动，在短短四年内，我们已经将情况转变为在英国的试验和实验医学文化。我们开发的关键活动&这些活动现在是有价值的英国可用资源：1.分层队列：有资格进入试验和研究的患者集合2。实验试验支持：能够在患者身上测试新疗法的协调和支持系统3。神经肌肉人类细胞生物库：收集患者的肌肉细胞以测试新的治疗方法4。核磁共振生物标记物研究：使用核磁共振扫描准确测量肌肉，并评估实验性治疗是否有效。培训方案，培训更多的年轻科学家进行试验和开发新疗法6。让临床医生和动物科学家密切合作，找出哪些是测试新疗法的最佳细胞和动物模型这些核心活动&我们的临床科学家网络使临床试验增加了十倍，参与研究队列的患者数量增加了更多。我们现在希望在这一成功的基础上，在英国的实践中嵌入试验文化。在英国，没有其他中心专注于系统地将NMD的发现研究与实验医学联系起来。在过去的四年里，这个MRC中心一直在领导英国的努力。一个更新的MRC中心的使命是通过将科学转化为实验医学来实现影响，并为患有致残性/致命神经肌肉疾病的成人和儿童找到治疗方法。

项目成果

Targeting protein homeostasis in sporadic inclusion body myositis.

• DOI: 10.1126/scitranslmed.aad4583
• 发表时间: 2016-03-23
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: 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
• 通讯作者: Greensmith L

The importance of genetic diagnosis for Duchenne muscular dystrophy.

• DOI: 10.1136/jmedgenet-2015-103387
• 发表时间: 2016-03
• 期刊: Journal of medical genetics
• 影响因子: 4
• 作者: Aartsma-Rus A;Ginjaar IB;Bushby K
• 通讯作者: Bushby K

Using a quantitative quadruple immunofluorescent assay to diagnose isolated mitochondrial Complex I deficiency.

• DOI: 10.1038/s41598-017-14623-2
• 发表时间: 2017-11-15
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Ahmed ST;Alston CL;Hopton S;He L;Hargreaves IP;Falkous G;Oláhová M;McFarland R;Turnbull DM;Rocha MC;Taylor RW
• 通讯作者: Taylor RW

Clinical, biochemical, and genetic spectrum of seven patients with NFU1 deficiency.

NFU1缺乏症患者的临床，生化和遗传谱。

• DOI: 10.3389/fgene.2015.00123
• 发表时间: 2015
• 期刊: Frontiers in genetics
• 影响因子: 3.7
• 作者: Ahting U;Mayr JA;Vanlander AV;Hardy SA;Santra S;Makowski C;Alston CL;Zimmermann FA;Abela L;Plecko B;Rohrbach M;Spranger S;Seneca S;Rolinski B;Hagendorff A;Hempel M;Sperl W;Meitinger T;Smet J;Taylor RW;Van Coster R;Freisinger P;Prokisch H;Haack TB
• 通讯作者: Haack TB