For millions of people worldwide living with osteoarthritis, the daily reality is defined by a slow, compounding erosion of comfort and mobility. Pain and stiffness make everyday activities—from climbing a flight of stairs to opening a jar—increasingly difficult as the condition gradually compromises independence. Common treatments available to patients today, ranging from over-the-counter pain relievers to localized steroid injections, may succeed in dampening symptoms for a temporary window of time, but they share a critical limitation. They do not alter the underlying trajectory of the disease or prevent the progressive structural damage occurring deep within the joint.
Now, innovative research originating from Yale University points toward an entirely different therapeutic approach. In a study recently published in the scientific journal Bioactive Materials, a team of investigators discovered that lacosamide—a medication already approved for human use—can fulfill a dual purpose in the context of osteoarthritis. According to the findings, the drug is capable of simultaneously mitigating joint pain and actively reversing cartilage damage. Furthermore, the therapeutic effects were shown to be exceptionally strong when the medication was delivered directly inside the joint space using a specialized, temperature-sensitive hydrogel designed to keep the drug localized.
Why Osteoarthritis Damages Cartilage
Osteoarthritis is frequently described in colloquial terms as a condition driven purely by mechanical wear and tear, but researchers emphasize that this simple characterization leaves out a vast and complex network of underlying biological processes.
Within the environment of a healthy joint, specialized cells known as chondrocytes work continuously to maintain the integrity of cartilage. They achieve this by striking a delicate, ongoing balance between the creation of new tissue and the orderly removal of older, degraded material. Osteoarthritis fundamentally disrupts this balance. Under pathological conditions, cartilage begins to break down at a pace far faster than the body can manage to replace it. Eventually, this progressive erosion thins the protective cushioning entirely, allowing raw bones to rub painfully against one another during movement. As the disease advances into its most severe stages, some patients ultimately require major joint reconstruction procedures, such as a total knee replacement, to restore function and relieve suffering.
"There is a major unmet need in osteoarthritis," notes 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 present, there is no single medicine approved by the U.S. Food and Drug Administration that possesses the capacity to both stop osteoarthritis pain and prevent or reverse the structural breakdown of articular cartilage. However, the work spearheaded by Liu and his research team suggests that it may soon be possible to address both of these clinical problems with a single, unified therapeutic strategy.
By successfully repurposing an existing medication and pairing it with an advanced biomaterial engineered to keep the drug concentrated within the joint, the researchers have outlined a potential path forward. This approach could preserve fragile joint tissue while delivering sustained, long-term pain relief without forcing patients to rely on systemic medications or addictive opioids.
A Protein Linked to Pain and Cartilage Loss
The investigative work centers heavily on Nav1.7, a specific protein that functions as a voltage-gated sodium channel. These sodium channels act as microscopic gates embedded within cell membranes, where they play a vital role in regulating electrical signaling throughout various tissues in the body.
For many years, the scientific community believed that Nav1.7 operated primarily within specialized nerve cells responsible for transmitting acute and chronic pain signals up to the brain. However, more recent investigative work conducted by Liu and his team revealed that this protein is also unexpectedly active within chondrocytes, the very cells tasked with maintaining and protecting cartilage.
In a healthy joint, Nav1.7 remains relatively quiet, showing minimal activity. In a joint afflicted by osteoarthritis, however, its behavior changes dramatically, with activity levels increasing substantially. The researchers discovered that this heightened protein activity not only intensifies localized pain signaling but also actively pushes chondrocytes toward breaking down the exact cartilage they would normally help preserve.
This dual involvement makes Nav1.7 an unusually promising therapeutic target, because it directly influences both the subjective sensation of pain and the physical, destructive 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 embarking on the lengthy and uncertain process of designing an entirely new chemical entity from scratch, Liu’s team decided to test existing drugs known to inhibit sodium channels. Among the various compounds evaluated, lacosamide emerged as the standout candidate, producing strong biological effects at considerably lower concentrations while offering a much more favorable safety profile than older, alternative drugs in the same pharmaceutical class.
Lacosamide is already widely recognized in clinical practice as an established treatment for epilepsy, but the Yale researchers uncovered a crucial nuance regarding its application: its effects on cartilage depend heavily on precise dosing parameters.
In this context, more was not necessarily better. At an ideal, relatively low concentration, lacosamide successfully encouraged cells to upregulate the production of structural proteins involved in building new cartilage while simultaneously suppressing the destructive biological processes that break tissue down. When the concentration deviated—becoming either too high or too low—those beneficial regenerative effects quickly began to fade away.
"This tells us the system is finely tuned," Liu notes, emphasizing the precision required. "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 biochemical investigation revealed that lacosamide also alters the fundamental ways in which cells communicate within the joint microenvironment. The drug was found to stimulate the release of two highly beneficial signaling proteins: HSP70 and midkine.
HSP70 is known to help cells respond effectively to cellular stress while actively supporting tissue repair mechanisms. Meanwhile, midkine helps regulate inflammation and protects vulnerable joint tissue from progressive degeneration. Together, these two proteins appear to create an optimal biological 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
While oral treatment with lacosamide proved effective during initial preclinical testing, administering drugs by mouth presents inherent challenges in clinical medicine. Systemic medications circulate broadly throughout the entire body, which inevitably increases the potential for unwanted side effects in unrelated organ systems.
To bypass this issue, the researchers investigated intra-articular injection, a method that allows medication to be placed directly inside the targeted joint space. Yet, this approach presented a significant physiological obstacle that required an innovative engineering solution.
"The knee joint, which is also the most common location for osteoarthritis, naturally acts like a leaky bucket," Liu says. "The body’s natural drainage system can clear out liquids injected into the knee within hours."
To keep the therapeutic medication in place for an extended duration, the team engineered a specialized hydrogel formulated from Collagen II. This advanced material possesses unique thermal-responsive properties. It remains in a fluid, liquid state while inside a cool syringe prior to administration, but quickly transforms into a firm, jelly-like matrix once it reaches normal human body temperature.
Once deployed inside the joint cavity, the gel functions as a localized storage depot for lacosamide. It holds the medication securely concentrated in the precise anatomical area where it is needed most, 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 subsequent preclinical studies, administering a single injection of the lacosamide-containing hydrogel every four weeks prevented structural cartilage loss far more effectively than administering a continuous oral dose every single day.
Existing Drug Could Speed Clinical Testing
One of the most consequential advantages of utilizing lacosamide is that the medication already holds regulatory approval for human use in other medical contexts. This established clinical safety record could make it possible to transition toward formal human clinical studies in osteoarthritis patients much more rapidly than would ever be feasible with a newly synthesized molecule.
Furthermore, lacosamide has already undergone human testing in patients suffering from specific nerve-related pain conditions linked directly to Nav1.7 mutations. Those prior human trials give the research team greater confidence that the promising biochemical effects observed in laboratory settings could eventually translate into meaningful, tangible pain relief for everyday patients.
The research also reflects a broader, highly anticipated direction in modern medicine that seeks to combine established pharmaceuticals with advanced biomaterials to maintain precise control over where and how treatments are delivered within the body. If this targeted approach ultimately proves successful in human clinical trials, it could eventually reduce the sheer number of invasive procedures patients must undergo, limit unwanted systemic side effects, and provide far longer-lasting biological 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."