A team of researchers at the Keck School of Medicine of University of Southern California (USC) have found a drug with the potential for curbing painful hyperinflammation from osteoarthritis, according to results of an animal study.
The findings indicate that a drug compound, R805/CX-011, may modulate an important cell receptor in the body’s immune system, GP130, that signals when antibodies should attack a virus or infection.
The animal model studies showed that the drug compound can disrupt the receptor’s over-activation of inflammation, and still manage pain and stiffness.
“We saw a profound effect on joint pain, structure and function,” said Denis Evseenko, Professor of Orthopaedic Surgery, Stem Cell Research and Regenerative Medicine at the Keck School of Medicine.
This year, the team will launch a combined Phase I and IIa trial of R805/CX-011 for the treatment of osteoarthritis in patients in collaboration with the start-up Carthronix.
Superior regenerative capabilities
The research by Evseenko and his colleagues suggests that blocking just one of GP130’s many signaling cascades, with either a drug or genetic modification, may prevent the hyper-inflammatory response that is the hallmark of osteoarthritis.
“In trying to fix the problem, the immune system causes even more damage,” said Evseenko. “But GP130 is a vital receptor. You cannot inhibit it, because it’s needed for healthy stem cells, as well as cardiovascular and immune function.”
The researchers genetically modified a mouse, substituting one amino acid for another in a way that prevents a specific GP130 signaling cascade from being activated.
The mouse showed signs of resistance to arthritis. It also showed superior healing and regenerative capabilities compared to other mice. For example, instead of healing skin wounds with a scar, the mouse appeared to completely regenerate new skin, including hair follicles, glands and other skin substructures.
Further studies in small and large animal models of osteoarthritis showed a clear “dose-dependent effect” that is critical for drug efficacy.
The team hopes that injections of R805/CX-011 may offer a less expensive, less invasive option that could be delivered several times a year in an outpatient clinic. They think the drug has the potential to delay or even reduce the need for joint replacement surgery, the only existing FDA-approved therapy for osteoarthritis.