Models, Mechanisms And Therapeutic Development Of Gator1-Related Epilepsies

Focal epilepsies account for two-thirds of all epilepsies. Focal cortical dysplasia, a malformation in the structure of the cerebral cortex, is a common factor underlying difficult-to-treat focal epilepsies. Focal cortical dysplasia is also associated with altered signaling in the mechanistic target of rapamycin (mTOR) pathway (of which the Gap Activity TOward Rags 1 – 1GATOR1 – complex is an inhibitor).

Utilizing a unique combination of methods including the use of human stem cells and genome editing methods to examine focal cortical dysplasia-related epilepsies in vitro (in culture) and in vivo (in live animals), Dr. Wang and his team will provide new insights into the mechanisms of focal cortical dysplasia and uncover useful platforms for drug discovery. Through this study, the team will gain conceptual insights broadly relevant to understanding not only focal cortical dysplasia but also for establishing the molecular mechanisms underlying other mTOR-based neurological diseases. The knowledge gained will guide the team towards the development of disease-modifying therapies with rational design, opening new avenues for therapeutic development.