Osteoarthritis in horses and in humans is a significant social and economic problem and continued research and improvements in therapy are needed. Because horses have naturally occurring osteoarthritis, which is similar to that of humans, the horse was chosen as a species with which to investigate gene transfer as a potential therapeutic modality for the clinical treatment of osteoarthritis. Using an established model of equine osteoarthritis that mimics clinical osteoarthritis, the therapeutic effects resulting from intra-articular overexpression of the equine interleukin-1 receptor antagonist gene through adenoviral-mediated gene transfer were investigated. In vivo delivery of the equine IL-IRa gene led to elevated intra-articular expression of interleukin-1 receptor antagonist for approximately 28 days, resulting in significant improvement in clinical parameters of pain and disease activity, preservation of articular cartilage, and beneficial effects on the histologic parameters of synovial membrane and articular cartilage. Based on these findings, gene transfer of interleukin-1 receptor antagonist is an attractive treatment modality for the equine patient and also offers future promise for human patients with osteoarthritis.
Bibliographical noteFunding Information:
This work was supported by the American Association of Equine Practitioners; College Research Council, Colorado State University; and the Southern California Equine Foundation. The authors would like to acknowledge Dr Rick D Howard for kindly providing phagemid containing the EqIL-1Ra gene and Heather Colhoun, Emily Sandler, Jennifer Goodnight, and the Veterinary Teaching Hospital’s Volunteer program for technical assistance, making this work possible.
- Gene therapy
- In vivo
- Interleukin-1 receptor antagonist