The goal of this project is to plan expanded in vivo characterization of the efficacy of “molecular tweezers” toward development of disease-modifying therapy for AD and related diseases.
This project addresses Alzheimer’s disease (AD) in the larger context of diseases caused by aberrant protein folding and self-assembly, which leads to formation of toxic oligomers and aggregates. In the last several years, Dr. Gal Bitan’s lab has been studying novel compounds called “molecular tweezers,” which modulate the aberrant assembly process using a previously unexplored “process-specific” mechanism. Their current lead compound effectively prevents formation of toxic aggregates of several disease-related proteins, including those involved in AD, Abeta and Tau. Initial in vivo experiments show peripheral administration of low doses of this compound lead to significant reduction of Abeta and Tau in the brain of transgenic mice.
In view of these promising data, they are poised to explore further the mechanism of action of the molecular tweezers and answer critical questions about their pharmacokinetics and safety.