Exploring Mitotherapy for Novel Treatment of Osteoarthritis in Horses

Osteoarthritis, an inflammatory degenerative condition affecting the whole joint, is a leading cause of lameness and attrition among performance horses. No existing treatments stop the progression of this disease, and none reverse the tissue degeneration. Still, researchers continue to look for new avenues to treat this painful condition.

“Many therapies are currently used in horses with osteoarthritis to help control inflammation and potentially slow disease progression. Examples include intra-articular corticosteroids and hyaluronic acid, oral hyaluronic acid, platelet-rich plasma, autologous conditioned serum, other biological therapies, as well as oral joint health supplements,” said Ashley Fowler, Ph.D., a nutritionist for Kentucky Equine Research.

Joint supplements, such as Synovate HA, work to proactively protect cartilage health by helping to maintain elasticity, enhance lubrication, and stimulate repair.

“Both older horses experiencing osteoarthritis and younger horses in exercise programs benefit from a joint supplement,” Fowler said.

Researchers are now exploring a new treatment for osteoarthritis. Defined as the transfer of functional mitochondria from a donor into “mitochondria-defective cells,” mitotherapy attempts to recover cell viability and prevent disease progression.

“Mitochondria are organelles central to energy metabolism and survival of the cell, and their dysfunction has been implicated in age-related and inflammatory disease. Mitochondria dysfunction has been documented in early- and late-stage osteoarthritis in chondrocytes (cartilage cells),” wrote the research team from the School of Veterinary Medicine, University of California, Davis.^*

“That research group also explained that cells in the synovial membrane of joints with dysfunctional mitochondria can release free radicals such as reactive oxygen species and nitric oxide that damage the extracellular matrix of cartilage and activate the inflammatory pathways, leading to osteoarthritis,” shared Fowler.

In a pilot study, researchers hypothesized that replacing dysfunctional mitochondria with exogenous mitochondria from a donor horse may “promote recipient cell rejuvenation and restore their functionality.”

The team isolated mitochondria from the platelets of healthy horses using a commercial kit. Three healthy horses were then recruited to be used as mitochondria recipients. The isolated mitochondria were resuspended in 1 mL of the recipient horse’s plasma. A synovial fluid sample was obtained from each recipient horse before injecting the mitochondria preparation into the joint. Synovial fluid samples were collected on days 1, 3, 7, 14, and 28 of the study.

“Results of this preliminary safety study were positive in that all horses remained healthy and no adverse reactions were noted. Specifically, no lameness or increased joint circumference indicative of inflammation were observed,” Fowler said.

Mild increases in nucleated cell counts and protein were appreciated in synovial fluid samples on days 1 and 3 following mitotherapy, but those changes did not reach statistical significance. Further, the synovial fluid parameters remained unchanged following treatment and could have been due to the local inflammation often seen when entering the synovial membrane (i.e., aspiration) rather than a reaction to the injected mitochondrial preparation.

“While minimal changes in systemic and local joint inflammation values were detected initially, these resolved without intervention within seven days. This safety information is critical moving forward with evaluating the potential for mitotherapy to treat synovitis and osteoarthritis,” concluded the researchers.

They added, “Based on our promising safety data, the next step would be to explore the efficacy of intra-articular mitotherapy in mitigating equine arthritis.”

^*Cassano, J.M., K. Marycz, M. Horna, M.P. Nogues, J.M. Morgan, D.B. Herrmann, L.D. Galuppo, and N. Vapniarsky. 2023. Evaluating the safety of intra-articular mitotherapy in the equine model: A potential novel treatment for osteoarthritis. Journal of Equine Veterinary Science 120:104164.