Lacosamide reverses cartilage damage in Yale study — SkimNews

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- Lacosamide — an FDA-approved epilepsy drug — reduced joint pain and reversed cartilage damage in preclinical osteoarthritis models, a dual effect no current FDA-approved therapy achieves, according to a Yale School of Medicine study published in Bioactive Materials (2026).
- The drug works by blocking Nav1.7, a sodium channel protein active in both pain-signaling nerves and chondrocytes; in osteoarthritic joints, Nav1.7 activity rises substantially, driving pain signaling and pushing cartilage cells toward tissue breakdown rather than repair.
- Cartilage effects were dose-dependent with a narrow optimal range — at ideal low concentrations lacosamide spurred production of cartilage-building proteins while suppressing tissue breakdown, but those benefits faded when concentrations ran too high or too low.
- The drug also triggered release of signaling proteins HSP70 and midkine, which support cellular stress response, tissue repair, and inflammation regulation, extending the drug's effects beyond individual cells to the broader joint environment.
- Researchers paired the drug with a Collagen II hydrogel that stays liquid inside a cool syringe but solidifies at body temperature, acting as an in-joint reservoir that gradually releases lacosamide over several weeks; one injection every four weeks outperformed daily oral dosing in preclinical tests.
- Principal investigator Chuan-Ju Liu, the Charles W. Ohse Professor of Orthopaedics & Rehabilitation, said lacosamide's existing FDA approval for epilepsy and prior human testing in Nav1.7-related pain conditions could compress the timeline to clinical trials in osteoarthritis patients.
- The approach also reflects a broader push to combine repurposed drugs with advanced biomaterials to control where and how treatments act, potentially reducing reliance on chronic pain regimens including opioids.
Why it matters: For the millions of people with osteoarthritis whose only options are pain medications that do not slow joint destruction, lacosamide's dual-action preclinical profile could compress the path to a disease-modifying therapy, since the drug is already FDA-approved for epilepsy with prior human safety data. A monthly intra-articular injection via the temperature-sensitive hydrogel could replace chronic oral pain regimens, including opioids, if the approach holds up in people.
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