Pathogenesis and treatment of the periodic paralyses

描述（由申请人提供）：周期性麻痹是罕见的神经肌肉疾病，是第一批由其特定基因突变定义的通道病。周期性瘫痪具有重叠的临床表型，但值得注意的是，致病基因病变涉及Na， K， Ca和CI通道。尽管关于每一种周期性麻痹的病理生理学信息丰富，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。周期性瘫痪具有遗传异质性，仍有许多患者的突变尚未被发现。虽然目前还没有针对任何周期性瘫痪的批准或标准治疗方法，但有一些合乎逻辑的候选药物适合临床试验。NINDS资助了一项治疗高钾血症和低钾血症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资助的一个项目侧重于开发针对最近出现的周期性麻痹——安德森-塔威尔综合征的新疗法。这笔拨款要求支持将在马里兰州贝塞斯达举行的为期两天的会议，该会议将汇集国际基础、临床神经科学家和非专业组织的代表，重点研究周期性瘫痪。会议的目标将是：(1)总结目前对周期性麻痹的病理生理学的认识，并重点关注其发病机制中尚未解决的难题；(2)考虑各种治疗策略的基本原理；(3)并考虑相对了解的周期性瘫痪如何为更广泛的通道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.