Repurposing FDA-Approved Therapeutics for Joint Regeneration
Medical research led by the Department of Orthopaedics and Rehabilitation at Yale School of Medicine has identified a potential breakthrough in treating osteoarthritis (OA)—a condition affecting hundreds of millions worldwide. Published in Bioactive Materials, the study highlights that lacosamide, an anti-seizure medication used for epilepsy, acts as a dual-action therapeutic capable of reducing pain and promoting cartilage restoration.
Current clinical management of osteoarthritis centers on temporary symptom relief through anti-inflammatory medications (NSAIDs), corticosteroid injections, or joint replacement surgery. The Yale findings position lacosamide as a potential Disease-Modifying Osteoarthritis Drug (DMOAD), addressing the underlying structural degeneration of the joint.
Overview: Key Scientific and Clinical Parameters
| Operational / Biological Metric | Detail & Research Findings |
| Research Institution | Yale School of Medicine (Department of Orthopaedics & Neurology) |
| Primary Target Molecule | $\text{Na}_{\text{V}}1.7$ Voltage-Gated Sodium Channel |
| Investigational Drug | Lacosamide (FDA-approved anti-epileptic medication) |
| Delivery Vehicle | Injectable Collagen II-based Hydrogel (Sustained 30-day release) |
| Key Secreted Biomarkers | HSP70 (Heat Shock Protein) & Midkine (Anti-inflammatory factor) |
Targeting $\text{Na}_{\text{V}}1.7$ Channels in Chondrocytes
The $\text{Na}_{\text{V}}1.7$ sodium channel was historically studied primarily for its role in pain-sensing sensory nerves. However, the Yale team discovered that $\text{Na}_{\text{V}}1.7$ is also overexpressed inside chondrocytes—the specialized cells responsible for maintaining cartilage integrity—during osteoarthritis progression.
Yale Osteoarthritis Therapeutic Pipeline: ---------------------------------------- Overactive Naᵥ1.7 Channel in Chondrocytes ──> Lacosamide Hydrogel Injection ──> Channel Blockade ──> Release of HSP70 & Midkine ──> Pain Relief & Cartilage RepairWhen overactive, $\text{Na}_{\text{V}}1.7$ drives chondrocytes to break down the surrounding extracellular matrix. By selectively inhibiting $\text{Na}_{\text{V}}1.7$ with lacosamide, researchers prompted cartilage cells to secrete protective signaling proteins—specifically HSP70 and midkine—which suppress inflammation and stimulate matrix synthesis.
Sustained Intra-Articular Delivery via Biomaterial Hydrogel
To optimize local therapeutic levels and prevent systemic central nervous system side effects associated with oral epilepsy medications, researchers formulated a bio-compatible Collagen II hydrogel.
In preclinical models, a single intra-articular hydrogel injection delivered once every four weeks provided longer-lasting cartilage protection and superior pain reduction compared to daily oral administration of the drug. Because lacosamide is already FDA-approved with an established human safety profile, the research team anticipates a streamlined pathway toward Phase I/II clinical trials in human subjects.





