REG-O3 is an innovative chimeric peptide combining a short amino acid sequence derived from growth hormone and an analog of somatostatin, both molecules involved in cartilage repair and anti-inflammatory processes, respectively. This peptide was therefore thought to show disease modifying osteoarthritis drug (DMOAD) potential and protect articular structure from osteoarthritis. This study aimed to investigate the DMOAD potential of REG-O3 by analyzing its effect on pain, joint function and structure, upon injection into osteoarthritic rat knee joint.
Osteoarthritis was induced in the right knee of mature male Lewis rats (n=12/group) by the surgical transection of the anterior cruciate ligament (ACLT) combined with the partial medial meniscectomy (pMMx). Treatments were administered intra-articularly (50µL) into the right operated knee from 14 days after surgery through 3 consecutive injections one week apart. REG-O3, solubilized in a liposomal solution, was injected into the right operated knee at either 5, 25 or 50 µg and compared to placebo (liposomal solution), and positive control items (dexamethasone [0.5 mg/kg], hyaluronic acid [HA, 1 mg/kg]). The study endpoints were the pain and function measured throughout the entire study once a week and the structure of the knee joint evaluated 8 weeks after surgery using OARSI score.
ACLT/pMMx surgery induced a significant decrease of right operated paw weight bearing in all groups. Compared to liposomal solution, REG-O3 was able to significantly improve weight bearing both as efficiently as dexamethasone and more potently than HA. When looking at cartilage histology, REG-O3 (25µg) was the only treatment able to significantly improve cartilage OARSI global score and to significantly reduce total cartilage degeneration width, cartilage matrix loss width and cartilage degeneration.
This study provides evidence of a remarkable protecting effect of REG-O3 on pain/joint function and cartilage/matrix degeneration in ACLT/pMMx model of rat osteoarthritis. REG-O3 displays an interesting profile as a DMOAD.