Funding Could Result in New Treatment for Rheumatoid Arthritis

UNC researchers Teresa Tarrant, M.D., and David Siderovksi, Ph.D., have been awarded a 2-year, $400,000 grant by the American College of Rheumatology to explore how a newly discovered protein – called GPSM3 – may serve as a potential target to treat inflammatory rheumatoid arthritis (RA).

The project represents an innovative merger between Tarrant’s clinical and translational research in RA and Siderovski’s basic science discoveries in complex molecular entities known as G protein signaling regulators. Virtually all cellular functions and a number of human diseases can be traced back to these mediators of cellular communication.

Tarrant and Siderovski used a $50K pilot award from the North Carolina Translational and Clinical Sciences (NC TraCS) Institute, home of UNC’s NIH Clinical and Translational Science Awards, to validate that the G protein signaling regulator GPSM3 has an important role in inflammatory arthritis. Their preliminary data with mice engineered to lack GPSM3 suggests that the development of acute inflammatory arthritis is blunted upon loss of GPSM3 function.

Their results indicated that this therapeutic effect came from disrupting the infiltration of large white blood cells or monocytes into the joints, a process central to the inflammation and joint destruction of RA. As Tarrant explains, targeting monocyte function by blocking GPSM3 would add a novel and potentially synergistic dimension to current RA therapies that include single cytokine neutralization (IL-1beta, IL-6, or TNFalpha) and cellular targeted therapy (rituximab).

Tarrant, an assistant professor of medicine and member of the Thurston Arthritis Research Center, and Siderovski, a professor of pharmacology, will use their new grant to further validate their findings and explore the potential of GPSM3 to treat RA. The grant comes from ACR’s “Within Our Reach” initiative, which is devoting $30 million to accelerate high-risk, high-reward research in inflammatory arthritis not normally funded by the National Institutes of Health or other peer-reviewed funding sources. This ACR program seeks to support projects that address basic, translational and clinical aspects of inflammatory arthritis.