Evaluating the Safety of Intra-Articular Mitotherapy in the Equine Model: A Potential Novel Treatment for Osteoarthritis

• Published in: Journal of equine veterinary science Vol. 120; p. 104164
• Main Authors: Cassano, Jennifer M., Marycz, Krzysztof, Horna, Marta, Nogues, Marcos Perez, Morgan, Jessica M., Herrmann, Daniel B., Galuppo, Larry D., Vapniarsky, Natalia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2023
• Subjects: Animals; Equine; Fibrinogen - metabolism; Fibrinogen - therapeutic use; Horse Diseases - drug therapy; Horses; Humans; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - veterinary; Injections, Intra-Articular - veterinary; Mitochondria; Mitotherapy; Osteoarthritis; Osteoarthritis - therapy; Osteoarthritis - veterinary; Synovial Fluid - metabolism; Synovitis; Synovitis; Mitochondria; Equine; Osteoarthritis; Mitotherapy
• ISSN: 0737-0806; 1542-7412
• DOI: 10.1016/j.jevs.2022.104164

•Osteoarthritis is a debilitating disease and new treatments are needed.•Mitochondria administration has the potential to halt the inflammatory cascade.•Intra-articular mitochondria did not induce systemic or local inflammation.•This safety information provides a basis to move to therapeutic efficacy evaluation.
No current treatments available halt osteoarthritis progression in horses or humans. Intra-articular injection of mitochondria is a novel treatment that has the potential to improve cell metabolism and decrease inflammation, but safety of this treatment has yet to be established in the horse. Autologous blood-derived mitochondria isolated using a commercially available kit were injected into the left carpus joint of 3 horses which were monitored for 28 days. Horses received physical examinations, video recorded gait evaluations, joint diameter measurement, synovial fluid collection, and blood collection on day 0 (baseline prior to mitotherapy, day of mitochondria injection), 1, 3, 7, 14, and 28. Systemic inflammation was assessed via complete blood count, fibrinogen, and plasma serum amyloid A (SAA). Local inflammation was assessed via synovial fluid cytology and physical examination parameters. Physical exam parameters remained stable and no joint swelling was observed after mitotherapy. No change was noted in video recorded gait evaluations as determined by a blinded evaluator. Complete blood counts revealed no significant increase in white blood cells. SAA only increased mildly in 1 horse. Fibrinogen became slightly elevated above reference range in 2 horses at day 7, but later normalized. Mild increases in synovial fluid nucleated cell counts and total protein occurred on day 1 and 3, but resolved within 7 days without intervention. Autologous mitochondria injection into the equine intercarpal joint was well tolerated with no signs of inflammation. This safety information allows for future studies evaluating mitotherapy efficacy.