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D. J. AGUIAR2, D. BRUNNER4, T. RUPP3, S. LEISER1, S. L. ROBERDS2


1PsychoGenics, Inc., Paramus, NJ, USA; 2Tuberous Sclerosis Alliance, Silver Spring, MD, USA; 3Porsolt, Le Genest-Saint-Isle, France; ;4Early Signal, New York.


The TS Alliance Preclinical Consortium seeks to inspire collaboration in TSC research by providing a forum for ideas, data and resource sharing to advance research from the bench to the clinic. The Consortium is a collaborative body of industry, academia and preclinical translation experts guided by the needs of TSC families to prioritize the evaluation of drug candidates chosen within known and novel mechanisms of action with the potential to make a difference in the lives of those affected by TSC. To this end, the Consortium requests drug candidate nominations twice a year from researchers for evaluation in mouse models of TSC. The TS Alliance established licenses to several mouse models of TSC tumors and seizures. The licenses provide rights to the Consortium members to conduct experiments under contract, to maintain confidentiality for commercial partners to protect their intellectual property, and to alleviate the need for industry partners to obtain individual licenses and establish animal models in their own labs. The Consortium currently has licenses to 2 mouse models of seizures: (1) TSC1-GFAP-CKO and (2) RhebCA; and 2 mouse tumor models: (1) TSC2null graft and (2) TSC2+/- kidney tumor model. Experiments are conducted at contract research organizations (i.e., PsychoGen¬ics and Porsolt) to ensure reproducibility and robustness of the models’ phenotypes and appropriate outcome measures. In addition to preclinical animal models of TSC, the consor¬tium provides other resources including access to cell-based models and animal models’ bio-samples, including serum and tissues, to test hypotheses and validate the relevance of a mechanism of action for TSC. The Consortium has already evaluated 30 compounds in TSC mouse models, leading to novel findings including the up-regulation of TLR4 and VEGF-D in brain and the ability of MEK inhibition to decrease seizures in the Tsc1-GFAP-CKO mouse and tumor burden in the TSC2null graft model. The Consortium’s strength relies in the expertise of academic and industry partners. It continu¬ously seeks to identify new partners and expand the breadth of TSC research, for example, including expanding research capabilities to evaluate TSC-associated neuropsychiatric disorders (TAND) in preclinical models and appropriate interventions.