For millions of people worldwide living with osteoarthritis, the daily reality is defined by a slow, painful deterioration of joint health. Everyday activities—from climbing a flight of stairs to walking around the block—grow increasingly difficult as stiffness and chronic pain set in. Traditional management options, ranging from over-the-counter pain relievers to localized steroid injections, have long offered only temporary relief. While these conventional methods can dull symptoms for a brief period, they do completely fail to address the root of the problem: the progressive, irreversible breakdown of the joint’s underlying structure.

Now, a promising new avenue of research emerging from Yale University suggests that a fundamental shift in how medicine approaches the disease may be on the horizon. In a study recently published in the scientific journal Bioactive Materials, a team of investigators discovered that an existing medication called lacosamide could serve a powerful dual purpose. Not only can the drug successfully reduce joint pain, but it also appears capable of reversing existing cartilage damage. According to the findings, these therapeutic effects are amplified significantly when the medication is delivered directly into the affected joint utilizing an advanced, specially engineered hydrogel.

Why osteoarthritis damages cartilage

Osteoarthritis is frequently dismissed in casual conversation as a simple condition caused by routine wear and tear over a lifetime. However, medical experts point out that this description glosses over the complex cellular biology that actually drives the disease.

Within a healthy human joint, microscopic cells known as chondrocytes are tasked with maintaining the integrity of the cartilage. They accomplish this by orchestrating a delicate, continuous balancing act: they simultaneously create new tissue to replace what is lost while removing old material. Unfortunately, osteoarthritis fundamentally disrupts this biological equilibrium. Once the disease takes hold, cartilage begins to break down at a much faster rate than the chondrocytes can possibly replace it. Over time, this progressive loss strips away the protective cushioning inside the joint, eventually allowing bare bones to rub directly against one another. As the condition advances to its later stages, many patients are left with few options other than invasive joint reconstruction procedures, such as a total knee replacement surgery.

"There is a major unmet need in osteoarthritis," explains 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, there is not a single medication approved by the U.S. Food and Drug Administration that possesses the ability to simultaneously stop the agonizing pain of osteoarthritis and halt or reverse the structural breakdown of joint cartilage. The groundbreaking work led by Liu and his research team suggests that it may soon be possible to tackle both of these massive clinical hurdles with a single, unified therapeutic strategy.

By successfully repurposing an existing medication and pairing it with a smart biomaterial designed to keep the drug localized inside the joint, the researchers have charted a path forward. This innovative approach could potentially preserve fragile joint tissue while delivering sustained, long-term pain relief, entirely bypassing the need to rely on addictive and potentially harmful opioids.

A protein linked to pain and cartilage loss

At the heart of the Yale study is a specific biological target known as Nav1.7. This particular molecule is a protein that functions primarily as a sodium channel. In biological systems, these sodium channels act as microscopic gates embedded within cell membranes, playing an essential role in the generation and transmission of electrical signaling throughout the body.

For many years, the scientific community operated under the assumption that Nav1.7 functioned almost exclusively within specialized nerve cells whose primary job was transmitting pain signals from the periphery up to the brain. However, more recent investigative work conducted by Liu and his dedicated team revealed a surprising twist: the protein is also remarkably active within chondrocytes, the very cells responsible for building and maintaining cartilage.

In a healthy joint, Nav1.7 remains relatively quiet and subdued. But when osteoarthritis develops and progresses, the activity of this protein ramps up substantially. The researchers discovered that this heightened, dysregulated activity does double damage. Not only does it intensify pain signaling pathways, but it also actively pushes chondrocytes toward breaking down the protective cartilage they would normally help preserve.

This dual involvement makes Nav1.7 an unusually promising and unique therapeutic target. Because the protein influences both the subjective sensation of physical pain and the objective physical deterioration of joint tissue, blocking it offers a way to address the two main symptoms of osteoarthritis simultaneously.

"When Nav1.7 becomes dysregulated, it contributes to both joint degeneration and pain," Liu notes. "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 expensive process of designing an entirely new chemical entity from scratch, Liu’s team decided to test existing medications that were already known to inhibit sodium channels. Among the various candidates evaluated in the laboratory, an epilepsy medication called lacosamide stood out by producing remarkably strong biological effects at significantly lower concentrations. Furthermore, it offered a notably superior safety profile compared to older, more traditional drugs within the same pharmacological class.

Lacosamide is already widely prescribed to human patients as a treatment for epilepsy, but the Yale researchers quickly discovered that its ability to heal cartilage depended heavily on a precise dosage.

In this context, more was not necessarily better. At an ideal, carefully calibrated low concentration, lacosamide successfully encouraged chondrocytes to produce the necessary proteins involved in building new cartilage while simultaneously suppressing the biological processes responsible for tissue degradation. However, if the concentration of the drug was either too high or too low, these beneficial therapeutic effects began to fade away entirely.

"This tells us the system is finely tuned," Liu observes. "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 deep-dive investigations into the cellular mechanisms revealed that lacosamide also alters the fundamental ways that cells communicate with one another within the tissue environment. The drug was found to stimulate the release of two highly beneficial signaling proteins: HSP70 and midkine.

HSP70 is known for helping cellular structures respond effectively to stress while providing robust support for tissue repair. Meanwhile, midkine assists in regulating harmful inflammation and shielding joint tissue from ongoing degeneration. Working together, this pair of proteins appears to create an internal biological environment that is vastly more favorable for the long-term maintenance and health of 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 testing lacosamide via oral administration proved effective during early preclinical trials, taking drugs by mouth presents a persistent clinical challenge. Oral medications must circulate systematically throughout the entire human body, which naturally increases the potential for unwanted side effects in unrelated organs and systems.

To circumvent this hurdle, the researchers turned their attention to intra-articular injections. This technique allows a medication to be placed directly inside the localized site of the problem—the affected joint itself.

Even so, a significant physical obstacle remained. "The knee joint, which is also the most common location for osteoarthritis, naturally acts like a leaky bucket," Liu points out. "The body’s natural drainage system can clear out liquids injected into the knee within hours."

To solve this dilemma and keep the medication in place for an extended period, the team engineered a specialized, temperature-responsive hydrogel constructed from Collagen II. This advanced biomaterial remains in a fluid, liquid state while inside a cool medical syringe, but rapidly transitions into a firm, jelly-like matrix once it reaches normal human body temperature.

Once safely inside the joint space, the innovative gel acts as a localized storage facility for the lacosamide. It holds the medication securely concentrated right where it is needed most, while gradually releasing the active compound over the course 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 course of preclinical studies, administering a single injection of the lacosamide-loaded hydrogel once every four weeks proved vastly more effective at preventing progressive cartilage loss than requiring patients to take a daily oral pill.

Existing drug could speed clinical testing

One of the most significant and practical advantages of utilizing lacosamide is the fact that the medication has already cleared rigorous regulatory hurdles and is approved for human consumption. This established safety record could potentially make it possible for researchers to advance toward human clinical trials involving osteoarthritis patients much faster than would ever be feasible with a completely novel pharmaceutical compound.

Furthermore, lacosamide has already undergone human testing in relation to certain nerve-related pain conditions triggered by specific Nav1.7 mutations. Those prior human data points give the Yale research team heightened confidence that the promising effects observed in laboratory settings could eventually translate into real, meaningful pain relief for everyday patients suffering from joint disease.

This line of investigation also mirrors a broader, modern shift within the medical field that increasingly pairs established pharmacological agents with advanced biomaterials to gain precise control over where and how treatments are administered in the body. If this targeted delivery method ultimately proves successful in human clinical trials, it could substantially reduce the number of invasive procedures patients require, limit systemic side effects, and offer much longer-lasting protection against permanent 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."