Novel Approach to Combating Osteoarthritis in Horses

Researchers have taken the first steps toward identifying a novel means of combating osteoarthritis, a common degenerative joint disease that limits the athletic careers and quality of life of horses. There is no cure for osteoarthritis, and the condition is invariably progressive. According to researchers, “There is an ongoing need to develop new therapeutic strategies aimed at the prevention and treatment of osteoarthritis.”^*

Current strategies for managing osteoarthritis include intra-articular corticosteroids, regenerative therapies such as platelet-rich plasma, nonsteroidal anti-inflammatory drugs such as phenylbutazone, and oral joint health supplements containing glucosamine, chondroitin sulfate, and hyaluronic acid.

“Oral joint supplements can help slow the progression of osteoarthritis but also work prophylactically for horses that do not yet show signs of the disease. Fish oil, a source of the long-chain polyunsaturated omega-3 fatty acids EPA and DHA, also benefits horses with osteoarthritis due to its anti-inflammatory properties,” said Ashley Fowler, Ph.D., a nutritionist with Kentucky Equine Research.

Looking to find new therapies for osteoarthritis, the researchers turned their attention to a molecule called cyclin-dependent kinase-9 (CDK-9). This molecule plays a role in producing inflammatory mediators involved in osteoarthritis. Laboratory and mouse studies show that inhibiting CDK-9 may be beneficial in reducing inflammation. Specifically, CDK-9 inhibitors prevent the transcriptional activation of inflammatory genes, which is a completely different anti-inflammatory mechanism provided by corticosteroids, joint supplements, and regenerative therapies.

The most widely studied CDK-9 inhibitor to date is a semi-synthetic molecule called flavopiridol.

To determine if flavopiridol could become an important tool in the management of osteoarthritis, a sustained-release formulation of flavopiridol was produced. This product was then injected into the middle carpal (knee) joint of four healthy horses. Synovial fluid was collected at weeks 0, 2, 4, and 6, and blood samples were collected weekly to measure flavopiridol concentrations in those fluids. Lameness exams were conducted weekly.

“Flavopiridol injections were well tolerated by all horses and no adverse events observed,” reported Fowler.

Detectable levels of flavopiridol were present in synovial fluid for at least four weeks, and peak flavopiridol levels were measured after one week. By five weeks, levels were undetectable. Flavopiridol was not detected in any blood samples.

“Next steps in developing this product for clinical use include dose-escalation studies to identify appropriate doses to administer and administering this product to horses diagnosed with joint disease,” Fowler said.

For supporting joint health, offer EO-3, a highly palatable supplement from Kentucky Equine Research that contains the long-chain polyunsaturated fatty acids EPA and DHA.

^*Katzman, S.A., D. Cissell, D. Leale, M. Perez-Nogues, M.D. Hall, G. Bloom, B. Hamamoto-Hardman, C. Wu, A.K. Haudenschild, G. Liu, J.H.N. Yik, and D.R. Haudenschild. 2024. Intra-articular injection of an extended-release flavopiridol formulation represents a potential alternative to other intra-articular medications for treating equine joint disease. American Journal of Veterinary Research: doi: 10.2460/ajvr.24.03.005.