Scientists have identified a compound with the potential to prevent the pathological changes that drive osteoarthritis and halt disease progression. In a study published today in ACS Omega, the researchers combined genomic analyses with AI-driven high-throughput screening to uncover a promising therapeutic candidate for a condition that still has no approved disease-modifying drugs.
Osteoarthritis is a chronic joint disease that causes persistent joint pain and impairs mobility, making it a leading cause of disability worldwide. Despite how common it is, there is no cure for osteoarthritis. Aside from joint replacement surgeries, current treatments are all palliative, providing symptomatic relief without preventing disease onset or slowing its progression.
“Our goal really comes down to treating patients,” said Michael J. Jurynec, PhD, associate professor of orthopedic surgery at University of Utah Health and senior author of the study. “Right now, the only thing we can do for osteoarthritis 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.”
In a previous study, Jurynec’s team identified rare variants of the WNK2 gene that underlie highly hereditary forms of osteoarthritis in families from the Utah Population Database. They showed that overactive WNK2 signaling in chondrocytes triggers inflammatory processes that increase susceptibility to osteoarthritis and promote disease progression.
Building on these findings, the researchers set out to look for compounds capable of inhibiting WNK2 as a potential treatment for osteoarthritis. Using an AI tool, they predicted the three-dimensional structure of the WNK2 protein and computationally screened hundreds of thousands of chemical compounds for their ability to bind the protein. This approach yielded more than 50 candidates predicted to bind and inhibit WNK2, which the team then narrowed down to six compounds through manual evaluation.
The researchers then tested the six candidates in a cell model of osteoarthritis, in which human chondrocytes are exposed to inflammatory conditions that mimic the disease environment. One of the compounds successfully prevented cellular changes associated with osteoarthritis, supporting its potential as a candidate for further therapeutic development.
“We treated cells with this new compound we discovered, and it inhibited many, many genes that are associated with osteoarthritis,” said Jurynec. “Not only did it inhibit these inflammatory factors, but it actually increased expression of genes that promote the health of these cells.”
Although these findings represent an important first step toward developing a new class of osteoarthritis treatments, further preclinical research will be needed before this candidate can be tested in clinical trials. Jurynec’s team is currently working with the University of Utah Therapeutics Accelerator Hub to develop improved versions of the compound to then test their safety and efficacy and animal models.
“This is really the beginning of the study, not the end,” said Jurynec. “We don’t have a drug that’s going to cure osteoarthritis yet, but this is very promising.”
