FDA-Approved Epilepsy Drug Shown to Reverse Osteoarthritis Damage in Yale Study

New research from Yale University suggests that lacosamide, an FDA-approved medication currently used to treat epilepsy, may offer a dual benefit for osteoarthritis patients by both alleviating pain and reversing cartilage degradation. The findings, published in the journal Bioactive Materials, highlight a potential shift from merely managing symptoms to modifying the progression of the disease.

Osteoarthritis is widely misunderstood as simple wear and tear, but the condition involves complex biological disruptions. In healthy joints, chondrocytes maintain a balance between creating new cartilage and removing old tissue. In osteoarthritic joints, this balance is lost, leading to rapid cartilage breakdown and bone-on-bone friction. Currently, no FDA-approved treatments exist that simultaneously stop pain and prevent structural joint deterioration.

Chuan-Ju Liu, PhD, the study’s principal investigator and Charles W. Ohse Professor of Orthopaedics & Rehabilitation at Yale, emphasized the urgency of the finding. “There is a major unmet need in osteoarthritis,” Liu said. “We need therapies that don’t just mask pain but actually change how the disease progresses.”

The study focuses on Nav1.7, a sodium channel protein previously thought to function primarily in pain-signaling nerves. However, Liu’s team discovered that Nav1.7 is also highly active in chondrocytes. In osteoarthritis, Nav1.7 becomes overactive, intensifying pain signals while driving the cells responsible for cartilage repair into a destructive mode. Blocking this protein appears to quiet pain nerves and encourage cartilage cells to stop breaking down tissue and begin repairing it.

Among several sodium channel inhibitors tested, lacosamide demonstrated strong biological effects at low concentrations with a favorable safety profile. The researchers found that the drug’s efficacy was dose-dependent; an optimal low concentration stimulated the production of cartilage-building proteins while suppressing tissue breakdown. Higher or lower doses diminished these benefits.

Further analysis revealed that lacosamide influences cell communication by stimulating the release of two signaling proteins: HSP70, which aids stress response and tissue repair, and midkine, which regulates inflammation and protects against degeneration. Together, these proteins create a supportive environment for cartilage maintenance across the entire joint tissue.

To maximize the drug’s effectiveness and minimize systemic side effects, the team developed a specialized temperature-sensitive hydrogel made from Collagen II. This gel remains liquid in a syringe but solidifies into a jelly-like state at body temperature. Acting as a local reservoir, the hydrogel releases lacosamide slowly over several weeks, keeping the medication concentrated within the joint.

Preclinical tests showed that a single intra-articular injection of the lacosamide-laden gel every four weeks was more effective at preventing cartilage loss than daily oral administration. Because lacosamide is already approved for human use and has been studied in patients with nerve-related pain conditions, the researchers believe clinical trials for osteoarthritis could proceed more rapidly than for novel drugs.

“We are not just developing a treatment,” Liu concluded. “We are developing a system that allows the medicine to work more effectively where it matters most. Our goal is to move beyond symptom control and towards true disease modification.”