Gamma-Secretase Modulators for Alzheimer's Disease

Michael Wolfe, PhD Brigham and Women's Hospital

Co-Principal Investigators

Corinne Augelli-Szafran, PhD University of Alabama at Birmingham


All of the specific aims in this research address one main goal: to identify gamma-secretase modulating drugs that are efficacious in a standard Alzheimer's disease transgenic animal model and suitable for pre-clinical drug development. The ultimate goal is to identify a drug candidate for the treatment of Alzheimer's disease.

Project Details

The goal of this project is to identify new agents that lower brain levels of amyloid, a protein widely thought to initiate Alzheimer's disease. We seek to accomplish this by selectively affecting an amyloid-producing enzyme so that this enzyme can continue serving a critical role it plays in normal human health. We have identified small, drug-like molecules that affect the enzyme in this way and now seek to advance them by (1) making variations of these molecules to optimize their selective effects on the amyloid-producing enzyme; (2) evaluating promising molecules for other properties that would suggest they might last long enough in the body be able to get where they need to be; (3) testing drug candidates in animal models for Alzheimer's disease; and (4) working toward the identification of backup drug candidates.