Nervous System Channelopathies: Pathogenesis and Treatment

描述（由申请人提供）：本申请响应RFA OD-08-001罕见疾病临床研究联盟（RDCRC）罕见疾病临床研究网络，并提出更新U54 # NS059065神经系统通道病变：发病机制和治疗，重点关注原型发作性疾病周期性麻痹，发作性共济失调和非营养不良性肌强直。它利用4个国家10个合作中心的优势，将分子科学家与在开发神经疾病新疗法方面经验丰富的临床研究人员联系起来。培训计划以转化科学家成功的指导技能为基础，培养一批面向患者的研究人员，为从事罕见病研究做好准备。神经通道病临床研究（CINCH）与美国和国际患者倡导组织建立了相互支持的关系：美国、加拿大和英国的MDA；国家共济失调基金会；4个美国CINCH中心最近资助了CTSAs；另外2个有crc （CTSA待定）。在英国，皇后广场国立医院调查员拥有6个新资助的转化研究中心之一，为研究和培训提供了丰富的基础设施，包括对一年的医科学生实习生的支持。新的CINCH项目将通过创新的试验设计，利用最初6年试点的新的患者报告的结果测量方法，来更好地表征发作性表型，并为Andersen-Tawil综合征、其他目前没有治疗选择的周期性瘫痪患者和发作性共济失调1设计治疗方法，从而解决发作性疾病的有效治疗靶点的开发。由其他基金资助的配套研究将描述通道功能障碍的生理含义，确定间歇性、复发性症状的风险/触发因素，并与行业合作伙伴合作将新的治疗药物推向市场。CINCH研究的见解有望为更好地理解许多其他发作性通道病（如癫痫和偏头痛）提供一个窗口；CINCH的学员将有能力为罕见病和常见病寻求创新的治疗方法。公共卫生相关性：本建议建立在最初资助周期中启动的纵向和治疗性临床研究的基础上。神经肌肉通道病的1、2期临床试验正在采用新的结果测量方法来确定治疗方法，并与行业合作伙伴和患者倡导团体合作，成功地将治疗方法带给患者。

DESCRIPTION (provided by applicant): This application responds to RFA OD-08-001 Rare Diseases Clinical Research Consortia (RDCRC) for the Rare Diseases Clinical Research Network and proposes the renewal of U54 # NS059065 Nervous System Channelopathies: Pathogenesis and Treatment, focusing on the prototypic episodic disorders periodic paralysis, episodic ataxia and nondystrophic myotonia. It exploits the strengths of 10 collaborating centers in 4 countries to link molecular scientists with clinical investigators experienced in the development of new treatments for neurological disease. The training plan builds on the successful mentoring skills of translational scientists to develop a cadre of patient-oriented investigators prepared for careers in rare disease research. The Clinical Investigation of Neurologic Channelopathies (CINCH) has mutually supportive relationships with US and international patient advocacy groups: the MDA's of the US, Canada, and UK; the National Ataxia Foundation; and the international Periodic Paralysis Association. 4 US CINCH centers have recently funded CTSAs; the other 2 have CRCs (CTSA's pending). In the UK the National Hospital Queens Square investigator has one of 6 newly-funded translational Research Centers providing a rich infrastructure for research and training including the support of year-out medical student trainees. New CINCH projects will address the development of validated therapeutic targets in episodic disorders with innovative trial designs using novel patient-reported outcome measures piloted in the initial 6 years to better characterize episodic phenotypes and to devise treatments for Andersen-Tawil syndrome, other periodic paralysis patients currently without treatment options, and episodic ataxia-1. Companion studies funded by other grants will characterize the physiologic implications of channel dysfunction, identify the risk/triggering factors for the intermittent, recurrent symptoms, and collaborate with industry partners to bring new therapeutic agents to market. Insights from CINCH investigations hold promise for providing a window for a better understanding of many other episodic Channelopathies such as epilepsy and migraine; CINCH trainees will be well-positioned to pursue innovative treatments for both rare and more common diseases. PUBLIC HEALTH RELEVANCE: This proposal builds on the longitudinal and therapeutic clinical studies that were initiated in the initial funding cycle. Phase 1,2 clinical trials for neuromuscular Channelopathies are employing novel outcome measures to establish treatment and working with industry partners and patient advocacy groups to successfully bring treatment to patients.