Gene Therapy for Osteoarthritis: IL-1Ra as a Disease-Modifying Agent in Animal Models

This study explores the potential of gene therapy for osteoarthritis treatment using a helper-dependent adenovirus (HDA) to administer interleukin-1 receptor antagonist (IL-1Ra) intraarticularly. The objective was to achieve long-term symptom relief and disease modification. Methods included evaluating HDA-IL-1Ra in mouse and horse models of osteoarthritis through histology, micro-computed tomography (micro-CT), thermal hyperalgesia tests, blood chemistry, synovial fluid and tissue analysis, and lameness assessments.

Results showed that in mice, HDA-IL-1Ra prevented cartilage damage and osteophyte formation, and reduced synovitis. Post-osteoarthritis induction treatment in mice improved cartilage status, increased cartilage volume and surface, and protected against thermal hyperalgesia. In horses, the therapy significantly improved lameness and showed improvements in cartilage and synovial membrane conditions, suggesting both symptomatic relief and disease-modifying effects.

The conclusion highlights the safety and efficacy of HDA-expressing IL-1Ra in treating osteoarthritis in both small and large animal models, establishing HDA as a promising vector for joint gene therapy.