Approved Drug Tackles Osteoarthritis in Large Animals

An approved blood thinning medication can treat osteoarthritis by targeting two molecules that drive the condition's inflammatory roots, according to new experiments involving mice and nonhuman primates. The results suggest that the drug, dabigatran, could address the lack of treatments that can modify or halt some of the core mechanisms of osteoarthritis, which is a leading cause of pain and disability worldwide. Research has linked the condition's progression to a chronic state of low-grade inflammation, which arises from inflammatory signaling molecules such as TNF-α and IL-1β. Although there are molecules that can inhibit each of these drivers individually, these single-target treatments have so far led to disappointing results in clinical trials. Wenyu Fu and colleagues theorized that targeting TNF-α and IL-1β in tandem could yield stronger therapeutic effects. They screened a library of FDA-approved drugs for compounds that could suppress both TNF-α and IL-1β signaling in human cartilage-producing cells, and identified the approved blood thinner dabigatran as a promising candidate. When given to mouse and macaque models of osteoarthritis, dabigatran relieved pain and slowed the degeneration of cartilage in the animals' joints. Follow-up experiments showed that dabigatran bound to a protein named BIG2, which indirectly dampened TNF-α's activity while boosting the degradation of the receptor for IL-1β. Fu et al. caution that further studies will be needed to establish dabigatran's safety due to its blood-thinning effects. Nevertheless, "further optimization of such compounds […] may facilitate translation of BIG2-directed modulation into therapeutic strategies for [osteoarthritis] and potentially other chronic inflammatory diseases," they conclude.