Nervous System Channelopathies: Pathogenesis and Treatment

本申请是对罕见病临床研究网络的RFA OD-08-001罕见病临床研究联盟（RDCRC）的回应，并建议更新U 54 #NS 059065神经系统脊髓病：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。它利用了4个国家10个合作中心的优势， 该项目旨在帮助各国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。该培训计划建立在转化科学家成功的指导技能的基础上，以培养一批为罕见疾病研究事业做好准备的以患者为导向的研究人员。 神经系统脊髓病临床研究（CINCH）与美国和国际患者倡导团体（美国、加拿大和英国的MDA;国家共济失调基金会;和国际周期性麻痹协会）有相互支持的关系。4个美国CINCH中心最近资助了CTSA;另外2个有CRC（CTSA正在申请中）。在英国，国家医院皇后广场调查员 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，包括对全年医学生学员的支持。新的CINCH项目将通过创新的试验设计，使用在最初6年中试行的新的患者报告的结局指标，以更好地描述发作性表型，并设计Andersen-Tawil综合征的治疗方法，目前没有其他周期性麻痹患者。 治疗方案和间歇性共济失调-1。由其他赠款资助的配套研究将描述通道功能障碍的生理影响，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调查的见解有望为更好地了解癫痫和偏头痛等许多其他发作性癫痫病提供一个窗口; CINCH学员将有能力为罕见和更常见的疾病寻求创新治疗。

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 includingthe 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.