For millions of people with osteoarthritis, pain and stiffness can make daily activities increasingly difficult. Common treatments, including over-the-counter medications and steroid injections, may reduce symptoms for a while, but they do not prevent progression of underlying joint damage.
New research from Yale suggests a different approach. In a study published in Bioactive materialsScientists have discovered that the drug lacosamide may serve two purposes in treating osteoarthritis: reducing joint pain while reversing cartilage damage. The effects were particularly strong when the drug was delivered directly into the joint using a specialized hydrogel.
Why osteoarthritis damages cartilage
Osteoarthritis is often referred to as a disease caused by wear and tear, but that description leaves out much of the biology involved.
In a healthy joint, cells called chondrocytes help maintain cartilage by continually balancing the creation of new tissue and the removal of old material. Osteoarthritis disrupts this balance. Cartilage begins to break down faster than it can be replaced, eventually allowing bones to rub against each other. As the disease progresses, some patients may eventually need joint reconstruction procedures, such as a total knee replacement.
“There is a major unmet need in osteoarthritis,” says the study’s principal investigator and Charles W. Ohse Professor of Orthopedics and Rehabilitation, Chuan-Ju Liu, PhD. “We need therapies that don’t just mask pain, but actually modify disease progression.”
Currently, no drug approved by the U.S. Food and Drug Administration can both stop osteoarthritis pain and prevent structural breakdown of cartilage. The work led by Liu suggests that it may be possible to address both problems with a single therapeutic strategy.
Researchers repurposed an existing drug and combined it with an advanced gel designed to keep the drug inside the joint. The approach could potentially preserve joint tissue while providing long-lasting pain relief without relying on addictive opioids.
A protein linked to pain and cartilage loss
The research focuses on Nav1.7, a protein that functions as a sodium channel. These channels act as microscopic gates in cell membranes and play an important role in electrical signaling.
Nav1.7 was long thought to operate primarily in specialized nerve cells that transmit pain signals to the brain. More recent work by Liu and his team, however, has revealed that the protein is also very active in chondrocytes, the cells responsible for maintaining cartilage.
Nav1.7 is relatively silent in healthy joints. On the other hand, in osteoarthritis, its activity increases considerably. Researchers have found that this increased activity can intensify pain signaling while also causing chondrocytes to break down the cartilage they would normally help preserve.
This makes Nav1.7 an unusual therapeutic target because it appears to influence both pain sensation and the physical deterioration of joint tissues.
“When Nav1.7 becomes dysregulated, it contributes to both joint degeneration and pain,” says Liu. “Our results suggest that Nav1.7 is a dual-action target. By blocking this unique protein, we can potentially soothe painful nerves and tell cartilage cells not only to stop breaking down, but also to start repairing themselves.”
Epilepsy drug shows potential for cartilage repair
Instead of creating an entirely new drug, Liu’s team tested drugs that already inhibit sodium channels. Among them, lacosamide produced potent biological effects at considerably lower concentrations and provided a better safety profile than older drugs in the same class.
Lacosamide is already used as a treatment for epilepsy, but researchers found that its effects on cartilage were highly dose-dependent.
More wasn’t necessarily better. At an ideal low concentration, lacosamide encourages cells to produce proteins involved in building cartilage while suppressing tissue breakdown processes. When the concentration was too high or too low, these benefits began to fade.
“This tells us that the system is perfectly tuned,” notes Liu. “There is an optimal range in which the drug helps restore balance without overcorrection. What stands out is not only its effectiveness, but also the low dose needed.”
Further investigation revealed that lacosamide also changes the way cells communicate. The drug stimulated the release of two beneficial signaling proteins, HSP70 and midkine.
HSP70 helps cells respond to stress and promotes tissue repair, while midkine helps regulate inflammation and protect joint tissues from degeneration. Together, proteins seem to create more favorable conditions for cartilage maintenance.
“These proteins create a favorable environment for the maintenance of cartilage,” explains Liu. “They allow the effects of the drug to extend beyond individual cells and influence entire tissues.”
Smart hydrogel keeps medication inside the joint
Oral lacosamide treatment has been shown to be effective in preclinical testing, but medications taken orally circulate throughout the body, increasing the risk of adverse effects elsewhere.
The researchers therefore studied intra-articular injection, which allows the medication to be placed directly inside the affected joint.
There was still one significant problem to overcome. “The knee joint, which is also the most common location for osteoarthritis, naturally acts like a leaky bucket,” says Liu. “The body’s drainage system can remove fluids injected into the knee within a few hours.”
To keep the drug in place longer, the team created a specialized hydrogel based on collagen II. The material reacts to temperature. It remains liquid inside a cold syringe, then becomes a firm, gelatinous material after reaching body temperature.
Once inside the joint, the gel acts as a storage site for lacosamide, keeping the drug concentrated in the affected area while gradually releasing it over several weeks.
“The hydrogel acts as a local reservoir,” says Liu. “It keeps the medication in place where it’s needed most and releases it slowly over time. It turns a daily pill into a long-lasting topical treatment that stays active for a month or more.”
In the same preclinical studies, an injection of the lacosamide-containing gel every four weeks prevented cartilage loss more effectively than taking a daily oral dose.
Existing drug could speed up clinical testing
An important advantage of lacosamide is that the drug is already approved for use in humans. This could make it possible to progress more quickly towards clinical studies in osteoarthritis patients than with a completely new drug.
Lacosamide has also been tested in humans with certain nerve pain caused by Nav1.7 mutations. These results give researchers greater confidence that the effects observed in laboratory studies could eventually translate into significant pain relief for patients.
This work also reflects a broader direction in medicine that combines drugs with advanced biomaterials to control exactly where and how treatments are delivered. If the approach proves effective in humans, it could potentially reduce the number of procedures patients need, limit unwanted side effects, and provide longer-lasting protection against structural joint damage.
“We are not just developing a treatment,” Liu concludes. “We are developing a system that allows the drug to work most effectively where it matters most. Our goal is to go beyond symptom control and achieve true disease modification. This effort brings us closer to that reality.”
Gn Health
