Small molecule could make a big difference for arthritis patients

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Small molecule could make a big difference for arthritis patients

LOS ANGELES – 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 a new publication in the Annals of Rheumatic Diseases, Evseenko’s team describes the promise of a new molecule aptly named “Regulator of Cartilage Growth and Differentiation,” or RCGD 423 for short.

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.

“The goal is to make an injectable therapy for an early to moderate level of arthritis,” says Evseenko, associate professor of orthopaedic surgery. “It’s not going to cure arthritis, but it will delay the progression of arthritis to the damaging stages when patients need joint replacements, which account for a million surgeries a year in the U.S.”

Evseenko sees RCGD 423 as a prototype for a new class of anti-inflammatory drugs with a very broad range of indications. His lab has already developed several structural analogs of RCGD 423 with varying biological effects and potency. In a previous study published in Nature Cell Biology, RCGD 423 was shown to activate stem cells to make hair grow. The lab is partnering with scientists at USC and beyond to explore the broader potential of these molecules to treat rheumatoid arthritis, jaw arthritis, lupus, neurological and heart diseases and baldness, as well as to maintain pluripotent stem cells in the laboratory.

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About the Keck School of Medicine of USC

Founded in 1885, the Keck School of Medicine of USC is among the nation’s leaders in innovative patient care, scientific discovery, education and community service. It is part of Keck Medicine of USC, the University of Southern California’s medical enterprise, one of only two university-owned academic medical centers in the Los Angeles area. This includes Keck Medical Center of USC, composed of Keck Hospital of USC and USC Norris Cancer Hospital. The two world-class, USC-owned hospitals are staffed by more than 500 physicians who are faculty at the Keck School. The school has more than 1,750 full-time faculty members and voluntary faculty of more than 2,400 physicians. These faculty direct the education of approximately 800 medical students and 1,000 students pursuing graduate and postgraduate degrees. The school trains more than 900 resident physicians in more than 50 specialty or subspecialty programs and is the largest educator of physicians practicing in Southern California. Together, the school’s faculty and residents serve more than 1.5 million patients each year at Keck Hospital of USC and USC Norris Cancer Hospital, as well as USC-affiliated hospitals, Children’s Hospital Los Angeles and Los Angeles County + USC Medical Center. Keck School faculty also conduct research and teach at several research centers and institutes, including the Eli and Edythe Broad Center for Stem Cell Research and Regenerative Medicine at USC, USC Cardiovascular Thoracic Institute, USC Institute of Urology, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, USC Norris Comprehensive Cancer Center, USC Roski Eye Institute and Zilkha Neurogenetic Institute.

In 2017, U.S. News & World Report ranked the Keck School among the top 35 medical schools in the country.

For more information, go to keck.usc.edu.

This study was supported by the National Institutes of Health under award number K01AR061415 and by the Department of Defense under award number W81XWH-13-1-0465. Fifty-three percent of the project’s funding was federally funded. Forty-seven percent of the project’s funding was not federally funded. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Defense.

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