Genomics and Future Drug Targets for Osteoarthritis Save

A Nature article details the results of an osteoarthritis, genome-wide association study meta-analyses across up to 489,975 cases and 1,472,094 controls, establishing 962 independent associations, 513 of which have not been previously reported. Results were published this week in the journal Nature.

By 2050, the total number of patients with osteoarthritis is estimated to reach 1 billion worldwide. There are no disease modifying therapies and current meds only manage symptoms like joint pain, stiffness and mobility issues.

“This is an exciting set of findings that have identified hundreds of potential new drug targets and opportunities for repurposing drugs already approved and on the market for other conditions,” said study co-author Marc C. Hochberg, MD, MBA, Professor Emeritus of Medicine at the University of Maryland School of Medicine. He has led studies focusing on the clinical epidemiology of osteoarthritis and other musculoskeletal disorders and also served as the Principal Investigator of the Baltimore Clinical Center for the Osteoarthritis Initiative and the Study of Osteoporotic Fractures.

The research team for the new Nature study highlight eight biological processes with convergent involvement of multiple effector genes, including the circadian clock, glial-cell-related processes and pathways with an established role in osteoarthritis (TGFβ, FGF, WNT, BMP and retinoic acid signalling, and extracellular matrix organization). They found that 10% of the effector genes express a protein that is the target of approved drugs, offering repurposing opportunities, which can accelerate translation.

“With 10 percent of our genetic targets already linked to approved drugs, we are now one step closer to accelerating the development of effective treatments for osteoarthritis," explains study leader Eleftheria Zeggini, PhD,  Director of the Institute of Translational Genomics at Helmholtz Munich and Professor of Translational Genomics at the Technical University of Munich.

Beyond identifying genetic targets with therapeutic potential, the study also provides valuable insights that could help tailor treatment strategies or potentially enable improved patient selection for clinical trials and precision medicine approaches.

The study, which included 87 percent of samples from those of European ancestry, was not statistically powered to identify novel signals in populations who were not of European descent.