The Mitochondrial Neurobiology and Therapeutics Lab, with continuous support from the Alzheimer Drug Discovery Foundation, is conducting an extensive drug discovery program that is entering the stage of lead optimization and the development of a preclinical drug candidate. The lab's mitochondria-targeted therapeutics discovery program is directed toward the prevention and treatment of neurodegenerative diseases — Alzheimer's disease in particular.
The lab's Discovery Funnel includes multiple primary and secondary assays that were specifically designed to allow a selection of best mitochondria-targeted small molecules based on the lab's understanding of the molecular mechanism of neuroprotection and the molecular target.
The Discovery Funnel is essential for the development of safe and efficacious treatment in humans because it allows research to develop molecules with high specificity and selectivity to the target.
Other assays in the Discovery Funnel confirm whether new molecules penetrate the blood-brain barrier, and could be safe for use in people. Final validation of new compounds in a transgenic mouse model of Alzheimer's disease provides data on safety and efficacy in cognitive protection.
Dr. Trushina and colleagues have demonstrated that partial inhibition of mitochondrial complex I activity using small molecules induced positive metabolic adaptation and a resistance to oxidative stress in primary mouse and human neuronal cells and in multiple mouse models of Alzheimer's disease.
Successful accomplishment of the lab's mitochondria-targeted therapeutics project could provide a disease-modifying strategy for currently incurable human conditions such as Alzheimer's disease.