Summit on Drug Discovery in Tuberous Sclerosis Complex and Related Disorders

描述(申请人提供)：此R13拨款申请申请资金，以支持定于2010年7月6-9日在华盛顿特区Omni Shoreham酒店举行的“结节性硬化症及相关疾病药物发现峰会”。峰会的目标是：“将结节性硬化症(TSC)研究界与其他在重叠研究领域工作的关键研究人员聚集在一起，促进思想的交流和建立合作关系”讨论我们目前的知识状况，确定关于用mTOR抑制剂治疗结节性硬化症和相关疾病的表现的知识差距，评估TSC和相关疾病的新药筛选项目的结果，以确定药物/化合物和未来临床试验的优先顺序，确定临床试验结果和用于TSC和相关疾病的未来临床试验的措施“回顾为TSC和相关疾病确定生物标记物的努力，LAM和相关疾病，可用作疾病进展和/或治疗效果的衡量标准。此外，海报会议将为更多的首脑会议与会者提供机会介绍他们的研究成果。工作组会议将讨论TSC和相关疾病的翻译研究中的研究机会和差距，以及临床试验结果，以及如何协调跨疾病实体的临床试验。旅行奖学金将根据对年轻研究人员提交的摘要的审查授予他们。自从TSC1/2基因及其蛋白产物在mTOR信号通路中的作用首先在果蝇中被发现，然后在哺乳动物系统中被证实以来，TSC、LAM及其相关疾病的研究进展令人印象深刻。这项研究是在2002年的TSC会议上刚刚出现的，得到了美国国立卫生研究院的支持，并导致了目前TSC和LAM的多中心临床试验。2007年，美国国立卫生研究院在马里兰州安纳波利斯举行了一次会议。本次会议报告了TSC临床试验的初步数据，以及来自TSC动物模型的重要新信息。2009年的会议提供了一个机会，展示临床试验的初步数据，以及TSC所有领域的基础和翻译研究。拟议的峰会将集中于药物发现和测试，评估我们在TSC、LAM和相关疾病中使用mTOR抑制剂的知识状况，并讨论哪些药物/化合物应该在细胞系和动物模型中进行测试，以及哪些药物/化合物准备转化为临床试验。有重要的研究机会需要讨论和解决，计划中的峰会将导致TSC、LAM和相关疾病的新合作和新的研究途径。 公共卫生相关性：结节性硬化症(TSC)是一种公共卫生问题，因为它是一种多系统遗传病，影响着50,000多名美国人和100多万人，不分性别、年龄、种族和民族。大多数TSC患者患有癫痫，超过50%的人有中度到重度的智力残疾和精神健康问题，包括抑郁、双相情感障碍、焦虑障碍和自闭症谱系障碍。这些人需要终身护理，并在他们的一生中依赖服务。

DESCRIPTION (provided by applicant): This R13 grant application requests funding to support the "Summit on Drug Discovery for Tuberous Sclerosis Complex and Related Disorders" scheduled for July 6-9, 2010 in Washington, DC at the Omni Shoreham Hotel. Objectives The objectives of the Summit are to: "Bring together the tuberous sclerosis complex (TSC) research community with other key researchers working in overlapping areas of research to foster cross-fertilization of ideas and the establishment of collaborations "Discuss the state of our current knowledge and identify knowledge gaps regarding treatment of the manifestations of TSC and related disorders with mTOR inhibitors " Assess results of new drug screening projects for TSC and related disorders to identify and prioritize the testing of drugs/compounds and future clinical trials " Identify clinical trial outcomes and measures to be utilized for future clinical trials for TSC and related disorders " Review efforts to identify biomarkers for TSC, LAM and related disorders that can be used as measures of disease progression and/or treatment efficacy. In addition, a poster session will provide an opportunity for additional Summit participants to present their research findings. Working Group meetings will allow for discussion of research opportunities and gaps in translational research in TSC and related disorders, as well as clinical trial outcomes and how clinical trials might be coordinated across disease entities. Travel scholarships will be awarded to young investigators based on review of their submitted abstracts. Since the role of the TSC1/2 genes and their protein products in the mTOR signaling pathway was identified first in Drosophila and then confirmed in mammalian systems, the research progress on TSC, LAM and related disorders has been impressive. This research was just emerging at the TSC conference in 2002, supported by the National Institutes of Health, and resulted in the current multicenter clinical trials for both TSC and LAM. In 2007, an NIH-supported conference was held in Annapolis, MD. Preliminary data from TSC clinical trials were reported at this meeting, along with significant new information from animal models of TSC. The conference in 2009 provided an opportunity for preliminary data from clinical trials to be presented, along with basic and translational research in all areas of TSC. The proposed Summit will focus on drug discovery and testing with an evaluation of the state of our knowledge about use of mTOR inhibitors for TSC, LAM and related disorders, as well as discussion of what drugs/compounds should be tested in cell lines and animal models, and what is ready to be translated into clinical trials. There are significant research opportunities to be discussed and addressed, and the planned Summit will lead to new collaborations and new research avenues for TSC, LAM and related disorders. PUBLIC HEALTH RELEVANCE: Tuberous Sclerosis Complex (TSC) is a public health concern because it is a multi- system genetic disease affecting more than 50,000 Americans and more than 1 million individuals of both sexes, all ages, races and ethnic groups. Most individuals with TSC have epilepsy, and more than 50% have moderate to severe intellectual disabilities and mental health issues including depression, bipolar disorder, anxiety disorder and autism spectrum disorder. These individuals require lifelong care and depend on services throughout their lives.