Small Molecule Prevents Cartilage Damage and Promotes Cartilage Repair; Scientists Will Pursue Further Investigation of Possible Treatment for Arthritis

Will there come a time when a patient with arthritis can forgo joint replacement surgery in favor of a shot? Keck School of Medicine of USC scientist Denis Evseenko, MD, PhD, has reason to be optimistic. In an article published online on February 7, 2018 in the Annals of Rheumatic Diseases, Dr. Evseenko's team describes the promise of a new molecule named "Regulator of Cartilage Growth and Differentiation," or RCGD 423 for short. The article is titled “Drug-Induced Modulation of Gp130 Signaling Prevents Articular Cartilage Degeneration and Promotes Repair.” The RCGD 423 molecule was identified in high-throughput screening of 170,000 small molecule compounds. As its name implies, RCGD 423 enhances regeneration while curbing inflammation. When RCGD 423 was applied to joint cartilage cells in the laboratory, the cells proliferated more and died less, and when injected into the knees of rats with damaged cartilage, the animals could more effectively heal their injuries. RCGD 423 exerts its effects by communicating with a specific molecule in the body. This molecule, called the glycoprotein 130 (Gp130) receptor, receives two very different types of signals: those that promote cartilage development in the embryo, and those that trigger chronic inflammation in the adult. RCGD 423 amplifies the Gp130 receptor's ability to receive the developmental signals that can stimulate cartilage regeneration, while blocking the inflammatory signals that can lead to cartilage degeneration over the long term. Given these auspicious early results, the team is already laying the groundwork for a clinical trial to test RCGD 423 or a similar molecule as a treatment for osteoarthritis or juvenile arthritis.
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