To spur development of new ideas leading to novel drugs, the TS Alliance funds research grants to help learn more about the mechanisms of pathology in TSC. To facilitate the translation of basic and mechanistic research into clinical trials and new treatments for TSC, the TS Alliance created a TSC Preclinical Consortium in collaboration with industry and academia to test the efficacy of candidate therapeutic drugs and advance the best to the clinical stage.
The Preclinical Consortium
The Preclinical Consortium engages academic researchers and pharmaceutical industry researchers in an effort to accelerate new compounds into the late stages of preclinical development. A Steering Committee sets the long-term goals, and Working Groups decide the best design for drug screening tests and provide oversight for rigorous quality control and interpretation of results. Compounds are handled and tested by experienced providers, and data are shared with all members of the consortium. Members belong to industry, academia, or nonprofit organizations. All members can propose compounds for the screen and benefit from the shared data.
The different manifestations of TSC — such as tumors in the lungs and kidneys as well as epilepsy — can be modeled in mice using different genetic manipulations. The Preclinical Consortium has chosen to use different models covering different aspects of TSC, namely epilepsy and tumors. The TSC1 GFAP conditional knockout mouse from Dr. Michael Wong’s lab will be used as model in which to test anti-epileptogenic and anti-epileptic compounds. The TSC2 heterozygous knockout mice from Dr. David Kwiatkowski’s lab will be used as a model of kidney tumors. Other models will be added as necessary for future studies.
Goals of the Drug Screen
The TSC Preclinical Consortium has several goals to ensure high quality of data and optimal use of models, assays, and R&D opportunities:
- Use standardized models, tests and assays for preclinical drug development
- Re-purpose compounds of interest
- Test analogs with improved safety profiles
- Investigate novel compounds and mechanisms of action
- Engage industry and increase opportunities for clinical trials
- Focus on transparency, robustness, replication, rigor and translatability
The TSC Preclinical Consortium is coordinated and wholly funded by the TS Alliance thanks to generous support from the Cowlin Family Fund, The Engles Collaborative Research Fund and many additional donors through the Unlock the Cure campaign.