Intra-articular injections of liposomal adenosine improve clinical outcomes and slow radiologic progression in a preclinical canine model of osteoarthritis

Objective: To test new, more stable and long-lasting formulations of liposomal adenosine in the treatment of OA in a preclinical canine model. Methods: OA was induced by arthroscopic medial meniscus release (MR) in the right knee (stifle) of purpose-bred hounds. Symptomatic OA developed by 2 months after which knees were injected monthly with 3 mL of saline or 2 different liposomal adenosine preparations, RgnA09M or RgnA09N, for a total of 3 injections. Blinded assessments of knee pain, function, comfortable range of motion (CROM) and effusion were performed before induction of OA, at 2 months, 4 months and at the time of sacrifice (6 months post-Tx). Radiographic assessments and MRI of the knees were also performed. Plasma and synovial fluid were collected and COMP and CTX-II levels assessed by ELISA. Results: Symptomatic OA developed by 2 months with increased pain, loss of function and diminished CROM. Saline treatment did not improve knee pain, CROM or loss of function at any time point but intraarticular injection of RgnA09M and RgnA09N markedly improved pain, CROM and function at all timepoints. Injections of RgnA09M and RgnA09N, but not saline, improved radiographic assessments at 4 months and 6 months. Similarly, MRI scores significantly improved in RgnA09M and RgnA09N treated dogs compared to saline. Histologic analysis showed that RgnA09M and RgnA09N injections reduced synovial inflammation. Conclusion: This is the first evidence that intraarticular injection of liposomal adenosine reduces pain, improves CROM and function and mitigates radiologic progression in a large animal OA model.