Yale researchers say that lacosamide osteoarthritis cartilage repair may be achievable with a single drug, used at low doses and delivered directly into the joint via a temperature-sensitive hydrogel. The study, published in Bioactive Materials, is preclinical: the results come from laboratory and animal models, not from human patients.
That caveat matters, because the claim being made is an ambitious one. At present, no drug approved by the U.S. Food and Drug Administration can both relieve osteoarthritis pain and halt the structural destruction of cartilage. The researchers, led by Chuan-Ju Liu, PhD, Charles W. Ohse Professor of Orthopaedics and Rehabilitation at Yale, say lacosamide could do both by targeting a single protein, Nav1.7, that appears to drive both pain signalling and cartilage breakdown.
What the study actually found
Nav1.7 is a sodium channel protein. In healthy joints, the researchers found, it is relatively quiet. In osteoarthritic joints, its activity rises, and the study’s authors argue this heightened activity does two things: it amplifies pain signals and it pushes chondrocytes, the cells that normally maintain cartilage, toward breaking tissue down rather than building it up. Blocking Nav1.7, the team reasoned, might address both problems at once.
Lacosamide, which Inc.com reports is commonly sold under the brand name Vimpat and has been FDA-approved for roughly 20 years, was already in use as an anti-seizure medication. Liu’s team selected it from a group of sodium channel inhibitors because it produced strong biological effects at low concentrations and showed a better safety profile than older drugs in the same class.
The dose question turned out to be critical. At an ideal low concentration, lacosamide encouraged chondrocytes to produce cartilage-building proteins while suppressing the processes that degrade tissue. Too high or too low, and those benefits diminished. The researchers also found that the drug stimulated the release of two signalling proteins: HSP70, which the study associates with cellular stress response and tissue repair, and midkine, which the authors link to inflammation regulation and protection of joint tissue. Together, the team says, these proteins may help create conditions that are more favourable for cartilage maintenance across the whole joint.
Oral lacosamide was effective in preclinical testing, but the researchers noted a practical problem: drugs taken by mouth travel throughout the body, not just to the affected joint. The knee, as Liu describes it, also acts as a kind of drainage system that can clear injected liquids within hours. To address both issues, the team developed a hydrogel made from Collagen II. The material stays liquid in a cool syringe and solidifies at body temperature, forming a slow-release reservoir inside the joint. In the preclinical studies, a single injection of the lacosamide-loaded gel every four weeks prevented cartilage loss more effectively than a daily oral dose.
The Nav1.7 connection and what human data exists
One reason the researchers are cautiously optimistic about translation to humans is that Nav1.7 has already been implicated in human pain conditions. A randomised, placebo-controlled, double-blind clinical trial published via NIH/PubMed Central found that lacosamide significantly alleviated pain in patients with Nav1.7 mutation-related small-fibre neuropathy. That is a different condition from osteoarthritis, and the result does not establish efficacy in joints. What it does provide is some human-level evidence that targeting Nav1.7 with lacosamide can have a measurable effect on pain, which strengthens the biological plausibility of the Yale team’s approach without confirming it.
Liu is direct about the gap that currently exists. ‘There is a major unmet need in osteoarthritis,’ he says. ‘We need therapies that don’t just mask pain but actually change how the disease progresses.’ The study’s framing positions lacosamide as a potential disease-modifying agent, not merely an analgesic, a claim that, if it holds in humans, would be a first for this condition.
Because lacosamide already has regulatory approval, Liu’s team says the path to clinical testing in osteoarthritis patients could be shorter than it would be for a novel compound. That is the standard argument for drug repurposing, and it is a reasonable one, provided the preclinical data continues to hold. The Yale School of Medicine team says the next step is moving the approach toward human studies, though no trial has yet been announced.
