Podium Presentation Osteoarthritis

16.1.9 - Novel Small Molecule Modulator of the gp130 Receptor shows Dose-Dependent Therapeutic Efficacy in a Canine Model of Osteoarthritis

Presentation Topic
Osteoarthritis
Date
14.04.2022
Lecture Time
12:09 - 12:18
Room
Bellevue
Session Type
Free Papers
Speaker
  • D. Evseenko (Los Angeles, US)
Authors
  • D. Evseenko (Los Angeles, US)
  • C. Flynn (Guelph, CA)
  • E. Lamoure (Guelph, CA)
  • B. Van Handel (Los Angeles, US)
  • N. Liu (Los Angeles, US)
  • M. Hurtig (Guelph, CA)
Disclosure
Denis Evseenko and Ben Van Handel are co-founders and significant shareholders in CarthroniX, Inc.

Abstract

Purpose

The pathogenesis of osteoarthritis (OA) often begins from an injury to articular cartilage, which establishes chronic, low-grade inflammation principally mediated by IL-6 family cytokines that signal through the obligate receptor gp130. However, we and others have shown that gp130 can also regulate anabolic responses in chondrocytes and immune system. Here, we unveil an advanced late pre-clinical regeneration-promoting candidate CX-011 that modulates, rather than completely inhibits, gp130 signaling.

Methods and Materials

Twenty-four purpose bred Foxhound dogs (12 females, 12 males), 10 months of age, (Marshall BioResources) were chosen for this study. All dogs underwent CT imaging of both knee joints then general anesthesia and arthroscopic surgery to induce OA by medial meniscal release (MMR). Three groups received CX-011 by intra-articular injection into the operated limb and the fourth control group (n=6) received an equal volume of vehicle. Injections were done four weeks post-operatively and again at 6 weeks after initial injection. The three experimental groups given the test article received doses of 10 μg, 1 μg or 0.1 μg in a 0.5 mL volume.

Results

Dose dependent effects of CX-11 were documented. In the highest dose of CX-011 (10 mg) group, there was highly significant chondroprotection (p = 0.012). Synovial inflammation was significantly limited by the two highest dose rates (p = 0.016) of the test article. CT imaging showed a dramatic, statistically significant reduction (p < 0.001) in shape alteration in dogs treated with the two highest dose levels of CX-011 compared to controls. Finally, the two highest doses had significantly reduced lameness, indicating lower pain levels with increasing test article concentration (p < 0.001).

Conclusion

The current study has nominated the gp130 modulator CX-011 as an excellent candidate for clinical progression as a disease modifying agent for OA with concurrent reduction in pain.

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