Pathogenesis and treatment of the periodic paralyses

描述（由申请人提供）：周期性麻痹是一种罕见的神经肌肉疾病，是第一种由其特定基因突变定义的通道病。 周期性麻痹有重叠的临床表型，但值得注意的是，致病基因病变涉及钠，钾，钙和CI通道。 尽管关于每种周期性麻痹的病理生理学的信息非常丰富，但仍然存在许多关于具有相似甚至相同突变的患者的表型变异的问题。 周期性麻痹是遗传异质性的，仍然有许多周期性麻痹患者的突变尚未被发现。 虽然没有任何周期性麻痹的批准或标准治疗方法，但有许多适合临床试验的逻辑候选人。 NINDS已经资助了一项多中心、随机、对照的高钾和低钾周期性麻痹治疗试验，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新的治疗方法，用于最近表征的周期性麻痹，Andersen-Tawil综合征。 这项赠款要求支持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理解，并关注有关其发病机制的未解决的困境;（2）考虑各种治疗策略的基本原理;（3）并考虑相对较好地理解周期性麻痹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.