Epilepsy Drug Lacosamide Shows Promise for Reversing Osteoarthritis Joint Damage

Osteoarthritis is often described as a wear-and-tear disease, but it involves an imbalance in cartilage-maintaining cells called chondrocytes, which normally balance building new cartilage against removing old tissue. In osteoarthritis, cartilage breakdown outpaces repair, eventually causing bones to rub against each other and sometimes requiring joint replacement. Current treatments such as over-the-counter pain relievers and steroid injections ease discomfort but do not slow that breakdown.

Researchers at Yale, led by professor Chuan-Ju Liu, found that lacosamide, a medication already approved by the U.S. Food and Drug Administration for epilepsy, both reduced joint pain and reversed cartilage damage in a study published in Bioactive Materials. The effect centers on Nav1.7, a protein that forms a channel enabling cells to send electrical signals. Nav1.7 was long thought to occur mainly in pain-signaling nerve cells, but the researchers found it is also highly active in chondrocytes, where it becomes overactive in osteoarthritis, amplifying pain and pushing the cells to break down cartilage.

Testing existing drugs that block the same channel, the team found lacosamide produced strong effects at low doses and had a better safety profile than older drugs in its class. At an optimal low concentration, it stimulated cartilage-building proteins while limiting tissue breakdown, and prompted cells to release two protective proteins, HSP70 and midkine, which support tissue repair and reduce inflammation.

Because oral lacosamide circulates throughout the body and raises the risk of side effects, the researchers also developed a thermoresponsive hydrogel made from Collagen II that stays liquid in a cool syringe but turns into a gel at body temperature once injected into the knee. The hydrogel released the drug gradually over several weeks, keeping it concentrated in the joint rather than being cleared within hours, as injected liquids normally are.