The Friedman Brain Institute Spring 2022

The Friedman Brain Institute Spring 2022

Welcome From the Director

FIVE OF THE top ten causes of disability worldwide are due to brain disorders. These include depression, stroke, dementia, psychosis, and drug addiction. Obesity (which involves strong brain-driven pathology) and chronic pain follow closely behind. Significantly, the social restrictions and isolation associated with the COVID-19 pandemic have made several of these conditions dramatically worse.

Yet, we have seen most large pharmaceutical companies reduce or even terminate their
investment in central nervous system (CNS) drug discovery in recent years, leaving an enormous unmet need.

Researchers at The Friedman Brain Institute (FBI) are doing their part in meeting this
need. In collaboration with Mount Sinai’s Drug Discovery Institute and several departments and other institutes on campus, our research teams are working to mine discoveries from the basic science laboratory for eventual clinical applications.

This issue of the FBI newsletter highlights current efforts focused around a class of proteins known as G protein-coupled receptors (GPCRs). They transduce the signals for most types of neurotransmitters, neuromodulators, growth factors, cytokines, and other stimuli.

GPCRs are among the most successful drug targets: It is estimated that as many as 40 percent of all medications in the Physician’s Desk Reference (a compilation of all drugs approved for use in the nation by the U.S. Food and Drug Administration) act on GPCRs. Yet, most GPCRs have not yet been successfully targeted for medicinal purposes.

Read how recent advances in using artificial intelligence/machine learning to virtually screen millions of compounds against selected GPCRs (taking advantage of so-called “biased signaling” that certain GPCRs exhibit) and adopting creative approaches to medicinal chemistry are promising paths to accelerate the drug discovery process. We also highlight novel approaches to CNS drug discovery that leverage today’s advances in genomics and epigenomics to generate treatments that are aimed at unconventional drug targets.

Nothing would have a greater, positive impact on humanity than conquering these illnesses, the ultimate goal of our efforts at the FBI.



Eric J. Nestler, MD, PhD

Eric J. Nestler, MD, PhD

Nash Family Professor of Neuroscience, Director, The Friedman Brain Institute, Dean for Academic Affairs, Icahn School of Medicine at Mount Sinai; Chief Scientific Officer Mount Sinai Health System