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.
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.