Pathogenesis and treatment of the periodic paralyses

描述(申请人提供)：周期性麻痹是一种罕见的神经肌肉疾病，是首批由其特定基因突变定义的经络疾病之一。周期性麻痹具有重叠的临床表型，但值得注意的是，致病基因损害涉及钠、钾、钙和CI通道。尽管关于每一种周期性麻痹的病理生理学的信息很丰富，但关于具有相似甚至相同突变的患者的表型变异仍然存在许多问题。周期性麻痹在遗传上是异质性的，仍然有许多周期性瘫痪患者的突变尚未被发现。虽然目前还没有针对任何周期性麻痹的批准或标准治疗方法，但有一些符合逻辑的候选药物适合临床试验。NINDS资助了一项治疗高钾和低钾周期性麻痹的多中心、随机、对照试验，该试验将很快开始招募。此外，Ord/NINDS资助的一个项目专注于开发治疗最近出现的周期性瘫痪--Andersen-Tawil综合征--的新疗法。这笔赠款请求支持在马里兰州贝塞斯达举行的为期两天的会议，这次会议将把国际基础、临床神经科学家和非专业组织的代表聚集在一起，重点研究周期性瘫痪。会议的目标将是(1)总结目前对周期性瘫痪的病理生理学的了解，并集中于关于其发病机制的尚未解决的困境；(2)考虑各种治疗策略的基本原理；(3)考虑相对较好的周期性瘫痪如何为更广泛的经络病研究领域提供信息。

DESCRIPTION (provided by applicant): The periodic paralyses are rare neuromuscular diseases which were among the first channelopathies to be defined by their specific gene mutations. The periodic paralyses have overlapping clinical phenotypes but remarkably, the causative gene lesions involve Na, K, Ca, and CI channels. Despite the wealth of information on the pathophysiology of each periodic paralysis there remain many questions concerning the phenotypic variation of patients with similar or even identical mutations. The periodic paralyses are genetically heterogeneous and there continue to be many patients with periodic paralysis whose mutations have not been discovered. While there are no approved or standard treatments for any periodic paralysis, there are a number of logical candidates suitable for clinical trials. NINDS has funded a multicenter, randomized, controlled trial of treatment of hyperkalemic and hypokalemic periodic paralysis that will begin enrollment soon. Moreover, an ORD/NINDS-funded project is focused on developing novel treatments for the recently-characterized periodic paralysis, Andersen-Tawil syndrome. This grant requests support for a two-day meeting to be held in Bethesda, MD that will bring together international basic, clinical neuroscientists and representatives of lay organizations with a research focus on the periodic paralyses. The meeting's goals will be (1) to summarize the current understanding of the pathophysiology of the periodic paralyses and focus on unresolved dilemmas concerning their pathogenesis; (2) to consider the rationale for various treatment strategies; (3) and consider how the relatively well understood periodic paralyses can inform the broader field of channelopathy research.