Yale Study: Repurposed Epilepsy Drug May Reverse Osteoarthritis Cartilage Damage

Researchers at Yale University published a study in the journal Bioactive Materials showing that the existing epilepsy medication lacosamide can reduce joint pain and reverse cartilage damage in osteoarthritis when delivered directly into the joint via a specialized hydrogel.

How Lacosamide Targets Nav1.7 Proteins to Protect Joint Tissue

Osteoarthritis disrupts the normal balance maintained by chondrocytes, which are cells responsible for preserving cartilage through the creation of new tissue and the removal of old material. As the condition advances, cartilage breaks down faster than it can be replaced, causing bones to rub together and frequently requiring joint reconstruction procedures like total knee replacements. The new Yale study focuses on Nav1.7, a protein functioning as a sodium channel that carries electrical signals. While traditionally thought to operate primarily in pain-transmitting nerve cells, Chuan-Ju Liu and his research team revealed that Nav1.7 is also highly active in chondrocytes during osteoarthritis.

When Nav1.7 becomes dysregulated, it intensifies pain signaling while pushing chondrocytes toward breaking down joint tissue. When Nav1.7 becomes dysregulated, it contributes to both joint degeneration and pain, Liu said, according to the findings. By inhibiting this protein, the medication can simultaneously quiet pain nerves and prompt cartilage cells to stop degrading while starting repair.

Our findings suggest that Nav1.7 is a dual-acting target. By blocking this single protein, we can potentially quiet the pain nerves and tell the cartilage cells to not only stop breaking down but start repairing as well.

Chuan-Ju Liu

Dosage Precision and Collagen II Hydrogel Delivery Systems

Instead of developing a new drug, the Yale team tested existing sodium channel inhibitors and found that lacosamide produced strong biological effects at lower concentrations with a better safety profile than older drugs. The medication’s effects depend heavily on dose concentration. At an optimal low concentration, lacosamide encourages cells to build cartilage proteins while suppressing tissue breakdown, a balance that fades if the concentration is too high or too low. The drug also stimulates the release of HSP70, which helps cells handle stress and repair tissue, and midkine, which regulates inflammation and protects joint tissue from degeneration.

Administering the treatment orally allows a drug to circulate throughout the body, raising the risk of unwanted side effects. To solve this, the researchers utilized intra-articular injection, though natural joint drainage typically clears injected liquids within hours. To keep the medication in place, the team designed a specialized hydrogel made from Collagen II. The material stays liquid inside a cool syringe and firms into a jelly-like state at body temperature, acting as a local reservoir that slowly releases lacosamide over a month or longer.

The hydrogel acts as a local reservoir. It holds the drug in place in the location it is needed most and releases it slowly over time. It transforms a daily pill into a long-lasting, local treatment that stays active for a month or longer.

Chuan-Ju Liu

Advancing Toward Human Clinical Studies for Joint Disease

Because lacosamide is already an approved medication for treating epilepsy and has undergone human testing for nerve-related pain conditions caused by Nav1.7 mutations, researchers can potentially move toward clinical trials in osteoarthritis patients more quickly than they could with a completely novel compound. Current treatments like over-the-counter medications and steroid injections only mask symptoms temporarily without altering disease progression. The combination of an existing drug with an advanced biomaterial aims to reduce unwanted side effects, decrease the frequency of medical procedures, and deliver long-lasting protection against structural joint damage.

We are not just developing a treatment. 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. This effort brings us closer to that reality.

Chuan-Ju Liu