For millions of people living with osteoarthritis, the daily reality of chronic pain and stiffness makes even the most ordinary activities increasingly difficult. Current medical options, ranging from over-the-counter pain medications to targeted steroid injections, offer temporary relief by subduing symptoms for a short duration. However, these traditional treatments fail to address the root of the problem, leaving the underlying joint damage to progress unchecked over time.
Now, a promising new study conducted by researchers at Yale University suggests an entirely different approach to managing and treating the condition. In findings published in the scientific journal Bioactive Materials, a team of scientists has discovered that the medication lacosamide can serve a dual purpose in treating osteoarthritis. The drug has been shown not only to reduce joint pain significantly but also to actively reverse cartilage damage. These therapeutic effects proved particularly powerful when the medication was administered directly into the affected joint using a specialized, temperature-sensitive hydrogel delivery system.
Why Osteoarthritis Damages Cartilage
Osteoarthritis is frequently described in everyday conversation as a condition caused simply by wear and tear, but that common characterization overlooks much of the complex biology involved in the disease’s progression.
Within a healthy joint, specialized cells known as chondrocytes help maintain and protect cartilage by continuously balancing the creation of new tissue with the removal of old material. Osteoarthritis disrupts this delicate biological balance. As the condition takes hold, cartilage begins to break down at a much faster rate than it can possibly be replaced by the body. Eventually, this progressive loss allows bones to rub directly against one another, causing severe discomfort, inflammation, and loss of mobility. As the disease advances into its most severe stages, some patients ultimately require major joint reconstruction procedures, such as a total knee replacement, to regain functionality.
"There is a major unmet need in osteoarthritis," says the study’s principal investigator, Chuan-Ju Liu, PhD, who serves as the Charles W. Ohse Professor of Orthopaedics & Rehabilitation at Yale. "We need therapies that don’t just mask pain but actually change how the disease progresses."
At the present time, no medicine approved by the U.S. Food and Drug Administration can simultaneously stop osteoarthritis pain and prevent the structural breakdown of joint cartilage. The groundbreaking work led by Liu and his research team suggests that it may soon be possible to address both of these critical problems with a single, unified therapeutic strategy.
By successfully repurposing an existing medication and pairing it with an advanced gel designed to keep the drug localized within the joint, the researchers have outlined an approach that could potentially preserve vital joint tissue while delivering sustained pain relief. Crucially, this method achieves its goals without relying on addictive opioids or other systemic drugs that carry heavy side effect profiles.
A Protein Linked to Pain and Cartilage Loss
The core of the Yale research focuses on a specific protein called Nav1.7, which functions primarily as a sodium channel. These sodium channels act as microscopic gates embedded within cell membranes, playing an essential role in regulating electrical signaling throughout the human body.
For a long time, the scientific community believed that Nav1.7 operated almost exclusively in specialized nerve cells responsible for transmitting pain signals from various parts of the body up to the brain. However, more recent work conducted by Liu and his laboratory team revealed that this same protein is also remarkably active in chondrocytes—the exact cells tasked with maintaining and repairing cartilage in human joints.
In healthy joints, Nav1.7 remains relatively quiet and subdued. In joints affected by osteoarthritis, however, its activity increases substantially. The researchers discovered that this heightened protein activity can intensify pain signaling while simultaneously pushing chondrocytes toward actively breaking down the cartilage they would normally help preserve.
This dual involvement makes Nav1.7 an unusual and highly valuable therapeutic target, because it directly influences both the subjective sensation of pain and the physical deterioration of joint tissue.
"When Nav1.7 becomes dysregulated, it contributes to both joint degeneration and pain," Liu explains. "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."
Epilepsy Drug Shows Potential for Cartilage Repair
Rather than spending years attempting to discover and synthesize an entirely new chemical entity, Liu’s team decided to test medications that already function as sodium channel inhibitors. Among the candidates evaluated, lacosamide produced remarkably strong biological effects at considerably lower concentrations and offered a significantly better safety profile than older, more conventional drugs within the same pharmacological class.
Lacosamide is already widely recognized and utilized as a treatment for epilepsy, but the researchers discovered that its effects on cartilage depended heavily on precise dosing.
More medication was not necessarily better. At an ideal, carefully calibrated low concentration, lacosamide encouraged cells to produce proteins actively involved in building new cartilage while simultaneously suppressing the cellular processes that break tissue down. When the concentration was either too high or too low, those beneficial therapeutic effects began to fade away.
"This tells us the system is finely tuned," Liu notes. "There is an optimal range where the drug helps restore balance without overcorrecting. What stood out was not just its effectiveness, but how little of a dose was needed."
Further investigation into the cellular mechanisms revealed that lacosamide also changes the fundamental ways that cells communicate with one another. The drug stimulated the localized release of two particularly beneficial signaling proteins known as HSP70 and midkine.
HSP70 helps cellular structures respond effectively to stress and supports overall tissue repair, while midkine helps regulate inflammation and protect vulnerable joint tissue from further degeneration. Together, these two proteins appear to create an internal environment that is far more favorable for maintaining and restoring healthy cartilage.
"These proteins create a supportive environment for cartilage maintenance," Liu explains. "They allow the effects of the drug to extend beyond individual cells and influence the entire tissue."
Smart Hydrogel Keeps the Drug Inside the Joint
During initial preclinical testing, oral treatment with lacosamide proved effective, but drugs taken by mouth circulate throughout the entire human body, increasing the potential for unwanted side effects elsewhere.
To circumvent this issue, the researchers investigated intra-articular injection, a method that allows the medication to be placed directly inside the targeted joint where it is needed most. However, this approach presented a significant physiological hurdle that the team needed to overcome.
"The knee joint, which is also the most common location for osteoarthritis, naturally acts like a leaky bucket," Liu says. "The body’s drainage system can clear out liquids injected into the knee within hours."
To keep the medication in place significantly longer, the research team engineered a specialized hydrogel made from Collagen II. This innovative material responds directly to temperature changes. It remains in a liquid state while inside a cool syringe, but then rapidly transforms into a firm, jelly-like substance once it reaches normal human body temperature.
Once inside the joint, the gel functions as a dedicated storage site for lacosamide. It keeps the medication highly concentrated in the affected area while gradually releasing the active compound over a period of several weeks.
"The hydrogel acts as a local reservoir," Liu says. "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."
In the same preclinical studies, a single injection of the lacosamide-containing hydrogel administered every four weeks prevented cartilage loss much more effectively than taking a daily oral dose of the medication.
Existing Drug Could Speed Clinical Testing
One of the most important practical advantages of utilizing lacosamide is that the medication is already fully approved by regulatory authorities for human use. This established safety record could make it possible to transition toward formal clinical trials in osteoarthritis patients much more quickly than would ever be possible with a completely novel drug compound.
Furthermore, lacosamide has already been tested in human subjects experiencing certain nerve-related pain conditions caused by specific Nav1.7 mutations. Those prior human trials give the research team greater confidence that the promising effects observed in laboratory and animal studies could eventually translate into meaningful, lasting pain relief for human patients.
This work also reflects a broader, forward-looking direction in modern medicine that combines proven pharmaceutical drugs with advanced biomaterials to control precisely where and how treatments are delivered in the body. If the approach ultimately proves successful in human clinical trials, it could eventually reduce the number of invasive procedures patients require, limit unwanted systemic side effects, and provide far longer-lasting protection against structural joint damage.
"We are not just developing a treatment," Liu concludes. "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."
