Northwestern researchers from the Center for Molecular Innovation and Drug Discovery (CMIDD) and the Feinberg School of Medicine (FSM) have received $1.16 million over the next three years from the National Institute of Mental Health (NIMH) to develop novel antidepressant therapies.
Researcher Assistant Professor and CMIDD Director of Chemistry, Gary Schiltz, PhD, and Dane Chetkovich, MD, PhD, Professor of Neurology and Physiology, have designed a screening and drug discovery approach towards a brain channel that could be targeted with small molecule inhibitors.
Dr. Chetkovich previously found that targeting a brain specific auxiliary subunit (TRIP8b) of the HCN channel is sufficient to disrupt HCN channel function and reduce depression-like behaviors in mice. While others have been interested in the HCN channel for new therapies, possible cardiotoxicities associated with targeting the HCN channel directly have precluded its study as a drug target. However, the work by Dr. Chetkovich has shown that by targeting the interaction of the HCN channel with TRIP8b, HCN channel function can be inhibited selectivity in the brain.
“Major depressive disorder (MDD) is a debilitating disease that affects 1 in 5 people worldwide,” said Dr. Schiltz. “Current treatments largely target neurotransmitters in the brain and have remained essentially unchanged for the last 50 years, even though up to half of all sufferers respond inadequately.”
This funding will support high-throughput screening using in vitro and in silico techniques to identify small molecules targeting this interaction. These hit compounds will then serve as starting points for further medicinal chemistry optimization with the goal of eventually developing new drugs to treat MDD.
“Through this award, we are targeting a novel molecular mechanism that has the potential to benefit a large population of people who urgently need new drug treatment options.”