Temple University College of Science and Technology (CST) has identified a potential next-generation chronic pain relief strategy that may offer safer alternatives to opioids. Based on a collaboration between CST and Genentech Inc. (Roche), the outcomes were published in the prestigious Proceedings of the National Academy of Sciences.
Researchers from Temple’s Institute for Computational Molecular Science (ICMS) have developed world-renowned expertise in the study of an ion channel called TRPA1, which generates the electrical signals, enabling the nervous system to sense pain.
It turns out that all cell membranes, even those with simple bacteria, are studded with ion channels, the proteins that are nature’s device for detecting environmental conditions and moving ions, or atoms or negative charge, into or out of the cell.
The Temple researchers used machine learning approaches to analyze TRPA1 ion channel across a wide variety of species. By focusing on the complex patterns of evolutionary mutations, they were then able to infer the principles underlying the functioning of TRPA1.
South San Francisco-based Genentech relied, in part, on this ICMS research developed at CST to design and synthesize molecules that target the TRPA1 ion channel. Temple researchers sought to test the Genentech developed molecules by using molecular simulations that would increase their potency and proposed a theoretical model for behavior for the molecules. Subsequent in vitro testing by Genentech has validated the hypothesis. A basic proof-of-concept testing in laboratory animals could occur as early next year.
The research was supported by Genentech, the National Institute of General Medical Sciences of the National Institutes of Health, and the National Science Foundation. The NSF, NIH and the U.S. Army Research Laboratory also funded Temple’s high-powered computing resources, which were used for computations.
CST Associate Professor of Biology Vincenzo Carnevale reports that given the worldwide opioid epidemic, to address chronic pain, we need to develop molecules that can offer relief to patients without the nasty side effects known to occur with opioids.” He continued, “Our goal is to inhibit pain signals in the nerve fibers where such signals originates—in your finger if you touch something hot, for instance—rather than treating it downstream in the central nervous system.”
· Vincenzo Carnevale, CST Associate Professor of Biology
· Jun Chen, Principal Investigator, Genentech
· Michael L. Klein, Professor of Science