Novel mTORC1 Inhibitors to Treat TSC
Abstract
Tuberous sclerosis complex (TSC) is a genetic disease that appears in early childhood. TSC is characterized by the growth of tumors in various organs, skin lesions, epileptic seizures, and cognitive deficiencies. The dysregulation of a protein called mTOR and its signaling pathway causes TSC (as well as other diseases such as cancer or diabetes). The mTOR protein occurs in two distinct protein complexes, called mTORC1 and mTORC2, which contain additional proteins, known as accessory proteins, and act upon distinct targets in the cell. Several mTORC1 inhibitors are approved for therapeutic use in the treatment of TSC. However, their use is often associated with undesirable side effects such as high blood glucose and cholesterol levels. This is because they fail to distinguish between mTORC1 and mTORC2 and eventually inhibit the function of both. Thus, the optimal approach for the treatment TSC through mTOR inhibition is a regimen that only inhibits mTORC1 without inhibiting mTORC2. The aim of the project is to find novel drug candidates that inhibit only mTORC1. This work will provide new clues on how mTORC1 works and will represent an entry point to develop drugs that specifically inhibit mTORC1 (and do not inhibit mTORC2) to treat TSC. This may in the future help TSC patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jun 29, 2021
- Source ID
- W81XWH2010240
Entities
People
- Michael N. Hall
Organizations
- United States Army
- University of Basel