Inherited Neurophathies Consortium (RDCRC)

描述(申请人提供)：Charcot Marie Tooth病(CMT)是遗传性周围神经病的代名词。这些是最常见的遗传性神经肌肉疾病之一，大约每2500人中就有一人受到影响。30多个基因的突变会导致CMT，另外40多个基因的基因位点已经被确定。CMT可分为三组：(1)CMT1，显性遗传性脱髓鞘神经病；(2)CMT2，显性遗传性轴索神经病；(3)CMT4，隐性遗传性神经病。许多形式的CMT都存在遗传上可信的动物模型，并提供了令人信服的数据，这些数据支持目前正在进行的CMT1 A人类临床试验。尽管有这些进展，但任何形式的CMT都没有有效的治疗方法，只有最常见的类型(CMT1A和CMT1X)的自然病史数据可用，许多潜在的基因-表型相关性仍然未知。为了解决这些问题，我们创建了遗传性神经病变联盟(HNC)，这是一个具有CMT专业知识的临床研究人员的集合。HNC内的网站包括韦恩州立大学、伦敦国家神经病学/神经外科医院、罗切斯特大学/肌肉研究小组(MSG)、宾夕法尼亚大学/费城儿童医院(CHOP)和佛罗里达迈阿密大学。将开展两个试点项目。威斯康星州立大学的吉拉·阿萨迪博士将在伦敦的蒙托尼博士和CHOP的芬克尔博士的帮助下，为CMT患者开发一种儿科评分系统。谢勒博士将为对CMT感兴趣的患者和研究人员开发一个效仿OMIM的网站。将实施两个临床研究项目。来自华盛顿州立大学的Shy博士将对CMT1B、CMT2A和CMT4A进行自然历史分析。来自迈阿密的Zuchner博士和Vance博士将搜索各种形式的CMT的修饰基因。来自伦敦的玛丽·赖利博士将领导一项针对博士后研究员和初级教职员工的培训计划，该计划将涉及包括味精在内的所有地点。来自罗切斯特的麦克德莫特博士将担任HNC生物统计学家。Charcot Marie Tooth Association(CMTA)、CMT UK(CMTUK)和Treat-NMD组织将与HNC广泛互动。与公共卫生相关：这些项目将提供对疾病机制的洞察，开发治疗方法，并教育未来的遗传性神经疾病研究人员。

DESCRIPTION (provided by applicant): Charcot Marie Tooth disease (CMT) is the eponym for heritable peripheral neuropathy. These are among the most common inherited neuromuscular diseases, affecting approximately 1 in 2500 people. Mutations in more than 30 genes cause CMT, and loci for more than 40 additional genes have been identified. CMT is separable into three specific groups: (1) CMT1, dominantly inherited demyelinating neuropathies; (2) CMT2, dominantly inherited axonal neuropathies; and (3) CMT4, recessively inherited neuropathies. Genetically authentic animal models exist for many forms of CMT, and have provided the data compelling the clinical trials in humans that are currently underway for CMT1 A. Despite these advances, no effective therapies are available for any form of CMT, natural history data are available for only the most common types (CMT1A and CMT1X), and many potential genotype-phenotype correlations remain unknown. To address these issues, we have created the Hereditary Neuropathy Consortium (HNC), a collection of clinical researchers with demonstrated expertise in CMT. Sites within the HNC include Wayne State University, the National Hospital for Neurology/Neurosurgery in London, the University of Rochester/Muscle Study Group (MSG), the University of Pennsylvania/Children's Hospital of Philadelphia (CHOP), and the University of Miami, Florida. Two Pilot Projects will be performed. Dr. Gyula Acsadi from WSU will develop a Pediatric Scoring System for CMT patients, aided by Dr. Muntoni from London and Dr. Finkel from CHOP. Dr. Scherer will develop a Website patterned after OMIM for patients and researchers interested in CMT. Two Clinical Research Projects will be performed. Dr. Shy, from WSU, will undertake a natural history analysis of CMT1B, CMT2A, and CMT4A. Drs Zuchner and Vance, from Miami, will perform a search for modifier genes in various forms of CMT. Dr. Mary Reilly from London will lead a training program for postdoctoral fellows and junior faculty members that will involve all sites including the MSG. Dr. McDermott, from Rochester, will be the HNC Biostatistician. The Charcot Marie Tooth Association (CMTA), CMT United Kingdom (CMTUK) and TREAT-NMD organizations will interact extensively with the HNC. PUBLIC HEALTH RELEVANCE: These projects will provide insights into disease mechanisms develop therapies and educate future investigators for the inherited neuropathies.