Gene Therapy for the Treatment of Equine Osteoarthritis

Abstract

Osteoarthritis (OA) is the predominant cause of lameness in horses. As in humans, the clinical symptoms of equine OA are persistent pain and dysfunction of the affected joint. Its pathology is similarly marked by progressive deterioration of the articular cartilage, subchondral bone sclerosis, marginal osteophytes, soft tissue inflammation and joint effusion. Disease pathogenesis is mediated by elevated levels of inflammatory cytokines and proteolytic enzymes in the articular tissues and synovial fluid. Existing pharmacologic agents can alleviate OA joint pain; none are able to inhibit erosive disease progression. As several gene-based treatments for human disease have received approval by the Food and Drug Administration (FDA), the transition to veterinary medicine will almost certainly follow. Several viral vector systems have demonstrated highly efficient gene transfer to the equine joint, enabling expression of therapeutic transgenes at efficacious levels for well over a year. Because of its large size, the equine joint is well suited to studies of gene-based therapies for arthritic disease. The forelimb joints are vulnerable to OA onset, and treatment and diagnostic modalities are the same in humans and horses. Here, we discuss the various gene-transfer approaches under investigation and the current progress toward the development an effective gene therapy for equine OA.