Allosteric modulation of voltage-gated sodium channels: Opportunities for neuropathic pain drug discoveries.
Rajesh Khanna, PhD
Professor, Department of Molecular Pathobiology
Director, NYU Pain Research Center
New York University, College of Dentistry
Pain remains a global health crisis. Despite extensive efforts by big pharma and academic labs worldwide, only opioids (new formulations of enhanced potency) have emerged clinically in the last few decades. While efficient for acute pain treatment, there is unanimous consensus that opioids are not recommended for treatment of long-term chronic pain. New, non-opioid, drugs are urgently needed. The NaV1.7 sodium channel is a prized target for pain therapeutics since mutations in the human gene, SCN9A, have been reported to produce both too much pain – due to gain-of-function mutations – or no pain – due to loss-of-function mutations. But despite these genetic links, development of NaV1.7 inhibitors has been unsuccessful due to reported lack of selectivity, insufficient channel blockade, and failure to engage NaV1.7-dependent endogenous opioid signaling. In this talk, Dr. Khanna will synthesize the history and discovery of this validated target, discuss the identification of NaV1.7 as a pharmacogenomic target, and illustrate the allosteric and gene therapy-based therapeutic potential of NaV1.7.
Rajesh Khanna, PhD, an internationally known expert in ion channels and pain research, was named director of the NYU Pain Research Center, effective January 1, 2022. Prior to joining NYU, Dr. Khanna was the associate director of the University of Arizona Health Sciences Comprehensive Pain and Addiction Center, a professor of pharmacology at the University of Arizona College of Medicine – Tucson, and a member of the BIO5 Institute. Dr. Khanna earned a PhD in physiology from the University of Toronto and completed a postdoctoral fellowship in the Department of Physiology and Cellular and Molecular Neuroscience at the University of California, Los Angeles. He has held faculty positions at the Toronto Western Research Institute, Indiana University—Purdue University Indianapolis, and the University of Arizona. He has authored more than 190 peer reviewed publications, directed the dissertations of five PhD candidates, and trained 20 postdoctoral fellows, and over a hundred undergraduates students. He serves as a grant reviewer for several NIH study sections and international funding agencies, is a reviewer for over 100 journals, serves as an Associate Editor of the Journal of Pain, and is an Executive Member of the North American Pain School. He holds several awarded patents and is the founder of 4 companies including Regulonix Inc. In 2020, he was elected as a Sr. member of the National Academy of Inventors.