mTORC1 is a central regulator of cell growth and metabolism. Its dysregulation is implicated in the development of tuberous sclerosis, a genetic disease associated with tumor growth in various organ systems. The aim of the Innosuisse funded feasibility study at the Biozentrum is to find novel drug candidates, which inhibit mTORC1 function to treat tuberous sclerosis and possibly other mTORC1-related disorders.
Rapalogs fail to completely inhibit mTORC1 and inhibit mTORC2 after prolonged treatment. mTOR kinase inhibitors affect both mTORC1 and mTORC2. mTORC2 inhibition leads to undesirable side effects. There is an unmet need for a truly selective mTORC1 inhibitor that can be used more broadly to treat chronic diseases caused by mTORC1 hyperactivation, such as tuberous sclerosis, without affecting mTORC2.
mTORC1 (mammalian Target of Rapamycin-Complex 1) regulates cell growth and metabolism. Its dysregulation can lead to multiple disorders including cancer, epilepsy, diabetes, as well as autoimmune diseases and age-related pathologies. Moreover, mTORC1 hyperactivation causes tuberous sclerosis. This genetic disease appears in early childhood and causes tumor formation in various organ systems, skin lesions, epileptic seizures and cognitive deficiencies.
The clinical application of current mTORC1 inhibitors is limited by a lack of overall effectiveness. This hinders the use of mTORC1 inhibition as a pharmacologic strategy to treat multiple conditions with unmet therapeutic needs. The scientists are now searching for drug candidates, which can provide a novel approach for specific mTORC1 inhibition. In a later phase, the most promising candidate will be developed into a drug to treat tuberous sclerosis and other mTORC1-related diseases.
With their project «Development of a lead compound for specific mTORC1 inhibition», the two project leaders Stefan Imseng and Asier González have ventured into entrepreneurship. The Swiss Innovation Agency Innosuisse will fund the study until 2020. Prof. Timm Maier und Prof. Michael N. Hall provide additional support for the scientists. The project findings will form the basis for a spin-off, providing the framework for the further development of drug candidates for clinical trials and their potential launch as drugs on the market.