Researchers are combining genetic studies of Utah families with artificial intelligence-based molecular biology tools to discover new medications that may help treat osteoarthritis at its source, according to an Aug. 6 report. Osteoarthritis is a chronic joint disease and a leading cause of disability, with current therapies focusing mainly on symptom management.
A newly identified drug compound has shown promise in promoting joint health and reducing inflammation-related genes in cell-based models of osteoarthritis. While the compound has not yet been tested for safety or efficacy in living organisms, it represents a starting point for developing innovative therapies targeting the disease process itself.
"Our goal really comes down to treating patients," said Michael Jurynec, PhD, associate professor of orthopedic surgery at University of Utah Health and senior author on the study. "Right now, the only thing we can do for OA is joint replacement or pain medication. So, if we can find something that slows down the disease process, giving people an extra 10 or 20 years of pain-free living, that's a huge advancement."
The research team used AI tools to narrow a pool of half a million drug candidates down to six within weeks. Previous genetic research had identified changes in the WNK2 gene as contributing to highly hereditary forms of osteoarthritis among some Utah families. Overactivity in this gene triggers inflammatory processes in joint cells; researchers believe blocking WNK2 could be an effective treatment approach.
Using AI-based predictions of protein structure and computational simulations with hundreds of thousands of chemical compounds, scientists generated a shortlist predicted to bind WNK2 and reduce its activity. Visual inspection further narrowed these candidates to six compounds. One candidate drug—referred to as M04—prevented osteoarthritis-related cellular changes and promoted cell health in laboratory models.
Jurynec said, "We treated cells with this new compound we discovered, and it inhibited many, many genes that are associated with osteoarthritis... Not only did it inhibit these inflammatory factors, but it actually increased expression of genes that promote the health of these cells." He emphasized more work is needed before clinical use: "This is really the beginning of the study... We don't have a drug that's going to cure OA yet. But this is very promising." The results appear in ACS Omega.
