Researchers at Yale University are investigating a new therapeutic approach to treat osteoarthritis. The active ingredient, lacosamide, is expected not only to reduce pain but also to slow the breakdown of cartilage. A special hydrogel could ensure that the medication remains effective for a longer period of time directly within the affected joint.
Why Osteoarthritis is More Than Just a Degenerative Disease
Osteoarthritis is one of the most common joint diseases and can significantly impair quality of life. Pain, stiffness, and increasing mobility limitations make everyday life difficult for many people affected by the condition. Current treatments focus primarily on alleviating symptoms. However, they cannot reliably halt the progressive loss of cartilage. A research team at Yale University in the U.S. is now pursuing a different approach. In a study published in the journal *Bioactive Materials*, scientists investigated the active ingredient lacosamide, which is already used to treat epilepsy. The preclinical results suggest that the drug may be involved in both the pain mechanisms and the biological processes that damage joint cartilage. Particularly promising was the combination with a special hydrogel that can release the active ingredient directly into the joint over an extended period following an injection.
Osteoarthritis is often described simply as a wear-and-tear disease. In reality, however, the processes occurring within the joint are significantly more complex. In this condition, the protective cartilage that covers the ends of the bones becomes increasingly damaged. Healthy cartilage tissue ensures that the bones can move against each other with as little friction as possible. At the same time, it cushions impacts and distributes the pressure exerted on the joint during everyday movements.
So-called chondrocytes play a central role in maintaining the cartilage. These specialized cells produce important components of the tissue and ensure that the processes of formation and breakdown normally remain in balance. In osteoarthritis, however, this balance is disrupted: the cartilage breaks down faster than the body can regenerate it. As the disease progresses, the tissue increasingly loses its protective function, which can lead to pain, stiffness, and limited mobility.
In advanced cases, joint damage can be so severe that a joint replacement becomes necessary. Although various treatment options are available—including pain relievers, physical therapy, and injections—these are primarily aimed at alleviating symptoms and improving mobility. To date, there are no established therapies involving medications that have been proven to halt the progression of the disease and restore damaged cartilage. This is precisely where the research by Chuan-Ju Liu and his team at Yale University comes in. The scientists are searching for ways to specifically intervene in the biological processes that influence both cartilage degradation and the development of pain. Their goal is not only to treat the symptoms but also to better protect the joint structure in the long term.
A sodium channel takes center stage in the research
The scientists focused on Nav1.7, a voltage-gated sodium channel. Such channels facilitate electrical signals within cells and play a key role in the transmission of pain signals. Nav1.7 is primarily known for its function in nerve cells. However, earlier studies by the research team showed that the protein is also active in chondrocytes.
According to the researchers, the activity of the sodium channel increases in osteoarthritis. This could have two problematic consequences: On the one hand, it may affect the processing of pain signals. On the other hand, changes in Nav1.7 activity appear to promote processes in the cartilage cells that contribute to tissue degradation. This opens up a potential treatment approach that not only influences pain perception but also targets the biological processes within the affected joint.
Lacosamide is Intended to Restore Balance in the Cartilage
Instead of developing a completely new active ingredient, the team investigated already known substances that affect sodium channels. In the process, lacosamide emerged as a promising candidate.
The drug is already used to treat certain forms of epilepsy. Preclinical studies showed that, at the appropriate dosage, it can promote processes that are important for the formation and maintenance of the cartilage matrix. At the same time, it inhibited mechanisms that contribute to tissue degradation.
The concentration of the drug was a key factor. The positive effects were particularly evident at a low, optimally adjusted dose. Higher or lower concentrations led to weaker results. This underscores how important precise dosing would be for its potential use in osteoarthritis. A higher amount of active ingredient does not automatically mean a better effect.
Two Signaling Proteins Could Support Tissue Repair
Additional studies provided clues as to how lacosamide might exert its effect on cartilage tissue. The drug influenced the release of two signaling proteins: HSP70 and midkine.
HSP70 belongs to a group of proteins that help cells respond to stress and maintain their functionality under stressful conditions. Midkine is involved in various biological processes, including the regulation of inflammatory responses and tissue protection mechanisms.
According to the study’s findings, both proteins may help create an environment that promotes cartilage preservation. The effect would thus not be limited exclusively to individual cells but could influence several processes that are important for the health of joint tissue. Further studies are needed to determine whether these mechanisms also have a clinically relevant impact in human joints.
Hydrogel is Designed to Keep the Active Ingredient in the Joint for Weeks
Another challenge is keeping the drug at the desired site for as long as possible. When taken orally, lacosamide is distributed throughout the body. As a result, the active ingredient can also reach tissues that are not intended to be treated.
An injection directly into the affected joint could improve local treatment. However, fluids injected into a joint are removed relatively quickly via natural drainage pathways.
To circumvent this problem, the researchers developed a hydrogel based on type II collagen. The material has temperature-dependent properties: at low temperatures, it remains liquid and can be injected. As soon as it warms to body temperature, it forms a gel-like structure.
Once inside the joint, the material is intended to serve as a local drug reservoir. It retains the lacosamide in the treated area and releases it gradually over an extended period. As a result, the treatment could maintain the drug concentration in the joint for longer without the need for daily medication.
Monthly Injections Showed Promising Results
In preclinical studies, the combination of lacosamide and hydrogel proved particularly promising. An injection of the drug-containing gel every four weeks prevented cartilage degradation in the models studied more effectively than daily oral administration. These results suggest that not only the active ingredient itself but also its targeted and time-controlled release could play an important role.
However, results from preclinical models cannot be readily extrapolated to humans. It remains to be seen whether the treatment will actually protect cartilage, reduce pain in the long term, and improve mobility in patients. Possible risks, the appropriate dosage, and the long-term tolerability of the combination of the drug and hydrogel must also be investigated.
An Already Approved Active Ingredient Could Facilitate Development
The fact that lacosamide is already approved as an antiepileptic drug could facilitate further development. Experience with the active ingredient in human use is already available. However, this does not mean that its efficacy and safety when injected directly into arthritic joints have already been proven.
For this new application, researchers must first demonstrate that the treatment approach is safe and offers real benefits for patients. This involves clinical trials that examine, among other things, pain, joint function, cartilage changes, and adverse side effects.
If the approach proves successful, it could make an important contribution to the development of so-called disease-modifying osteoarthritis therapies. These therapies are designed not only to alleviate symptoms but also to influence the progression of the disease.
Further Research Approaches for Cartilage Regeneration
Other scientific studies are also exploring new ways to protect damaged articular cartilage and promote its regeneration. A systematic review with a meta-analysis published in 2025 in the *Journal of Orthopaedic Surgery and Research* examined decellularized extracellular matrix (dECM) for this purpose. This is a biological scaffold material that retains important structures and components of the original tissue after the cells have been removed.
The analysis of ten preclinical studies suggests that such materials could support cartilage repair. They are thought to provide cells with a suitable environment to build tissue and promote regenerative processes. However, the results are based on animal studies, and the studies examined showed significant differences in some cases. Whether these approaches are suitable as effective long-term treatments for people with osteoarthritis must therefore still be tested in clinical trials.
New hope – But Not Yet a Breakthrough in Treatment
The research findings from Yale open up new possibilities for the treatment of osteoarthritis. The active ingredient lacosamide could not only relieve pain but also slow the breakdown of joint cartilage and help preserve it. When combined with a special hydrogel, the medication is designed to remain directly in the affected joint for a longer period and be released there gradually.
If this approach proves successful, it could represent a major advance. Current treatment methods focus primarily on relieving pain and stiffness. The new strategy, however, aims to influence the biological processes responsible for progressive cartilage loss. At the same time, the controlled release of the active ingredient could reduce the need for frequent injections.
However, further research is needed before it can potentially be used in humans. The results to date come from preclinical studies. Whether lacosamide can actually repair cartilage damage, reduce pain in the long term, or delay joint surgery must first be demonstrated in clinical trials. The safety and tolerability of the treatment during long-term use also need to be investigated more closely.
The results therefore represent a promising research approach, but not yet a medical breakthrough. They do, however, show that the combination of already known active ingredients and innovative biomaterials could open up new avenues in osteoarthritis therapy. The key will be whether the observed effects can be confirmed in patients in the future.