Lacosamide osteoarthritis therapy may offer a way to ease pain while helping joints heal, according to new research from Yale. In laboratory and preclinical models described in the journal Bioactive Materials, investigators report that the epilepsy medication reduced pain and helped restore cartilage, with the strongest effects seen when the drug was injected into the joint using a specialized hydrogel.
Lacosamide osteoarthritis approach targets biology of cartilage loss
Osteoarthritis is often described as wear and tear, but the disease involves a breakdown in the normal activity of chondrocytes, the cells that maintain cartilage. When this balance falters, cartilage deteriorates faster than it is replaced, eventually allowing bone-on-bone contact. Advanced cases can lead to surgical reconstruction, including total knee replacement.
“There is a major unmet need in osteoarthritis,” said principal investigator Chuan-Ju Liu, PhD, Charles W. Ohse Professor of Orthopaedics & Rehabilitation. Liu said new therapies should aim to change the course of disease rather than only dull pain. No U.S. Food and Drug Administration approved medicines currently both relieve osteoarthritis pain and prevent the structural breakdown of cartilage, the team noted.
The researchers repurposed an existing medicine and paired it with an engineered gel designed to keep the drug inside the joint. The strategy is intended to preserve tissue and provide sustained pain relief without reliance on opioids.
A sodium channel linked to pain and cartilage degradation
The work centers on Nav1.7, a sodium channel that helps regulate electrical signaling. Long studied in sensory neurons that transmit pain, Nav1.7 is also highly active in chondrocytes, the Yale team reported. In healthy joints the channel is relatively quiet. In osteoarthritis, its activity rises, which the researchers found can amplify pain and drive chondrocytes toward breaking down cartilage.
Because Nav1.7 appears to influence both pain sensation and cartilage deterioration, the team identified it as a potential dual-action therapeutic target.
“When Nav1.7 becomes dysregulated, it contributes to both joint degeneration and pain,” Liu said. “By blocking this single protein, we can potentially quiet pain nerves and prompt cartilage cells to slow breakdown and begin repair.”
Epilepsy drug shows dose-dependent cartilage benefits
Rather than design a new compound, the group evaluated existing sodium channel blockers and found that lacosamide produced strong effects at comparatively low concentrations and with a favorable safety profile relative to older agents. Already used to treat epilepsy, lacosamide’s cartilage effects depended on dose in the lab.
At an optimal low concentration, the drug increased production of cartilage-building proteins and dampened pathways that drive tissue breakdown. Benefits waned when the dose was too high or too low, suggesting a narrow therapeutic window. Liu said the findings indicate a finely tuned system in which small amounts may restore balance without overcorrection.
Further experiments showed lacosamide altered cell-to-cell communication by stimulating the release of HSP70 and midkine. HSP70 supports stress responses and repair, while midkine regulates inflammation and helps protect joint tissue. Together, these signals appeared to foster a tissue environment more supportive of cartilage maintenance.
Hydrogel delivery keeps the drug in the joint longer
Oral lacosamide reduced symptoms in preclinical testing, but systemic dosing circulates drug throughout the body. The team therefore explored intra-articular injection to place the medication directly in the affected joint. Because fluid injected into the knee can drain within hours, the researchers developed a Collagen II hydrogel that remains liquid in a cooled syringe and gels at body temperature.
Once injected, the temperature-responsive hydrogel acts as a depot that concentrates lacosamide in the joint and releases it gradually over weeks. In the same preclinical studies, a single injection of the lacosamide-loaded gel every four weeks prevented cartilage loss more effectively than a daily oral dose, the team reported.
Existing approval could accelerate clinical testing
One advantage of lacosamide is its existing approval for use in people for epilepsy, which could expedite movement toward clinical studies in osteoarthritis patients, according to the researchers. The drug has also been tested in people with certain Nav1.7-related pain conditions, lending support to the idea that laboratory findings might translate to meaningful pain relief.
The work reflects a broader trend in combining medicines with biomaterials to control where and how therapies act. If confirmed in human studies, the approach could reduce procedures, limit side effects, and offer longer-lasting protection against structural joint damage.
“We are not just developing a treatment,” Liu said. “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 toward disease modification.”
The preclinical models used in this research align with a wider scientific effort to reduce reliance on animal experiments, as seen in emerging alternatives to animal testing in drug development. Researchers hope such systems will speed translation of promising laboratory findings into safer, more targeted therapies for patients.