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Wednesday, August 14, 2013

MORGANTOWN, W.Va. – The Centers for Disease Control and Prevention report that approximately 480,000 West Virginians suffer from arthritis, the most common cause of disability in the U.S. New research out of the West Virginia University School of Medicine may eventually lead to new drugs that could help relieve arthritis sufferers’ pain and joint damage.

David Siderovski, Ph.D., the E.J. Van Liere Endowed Professor and Chair of the WVU Department of Physiology and Pharmacology, is the senior author on a National Institutes of Health-funded study published in an upcoming issue of the Journal of Leukocyte Biology titled “G protein-coupled receptor kinase-3 deficient mice exhibit WHIM syndrome features and attenuated inflammatory responses.”

WHIM syndrome (Warts, Hypogammaglobulinemia, Infections and Myelokathexis syndrome) is a rare, congenital disease of the immune system. Dr. Siderovski and his research colleagues found that a mouse strain with similar genetic problems to patients with WHIM syndrome had a built-in protection against arthritis development because a particular gene – GRK3 – was missing. As a result, Siderovski believes that developing a drug to inhibit GRK3 could help decrease arthritis in humans.

This research falls in line with additional research Siderovski and colleagues published in the journal Molecular Immunology in June. In that paper – “G-protein signaling modulator-3, a gene linked to autoimmune diseases, regulates monocyte function and its deficiency protects from inflammatory arthritis” – the team determined that mice lacking another gene, GPSM3, were also protected from developing arthritis.

Research into GPSM3 has now led to collaboration between Siderovski’s lab and Colleen Watkins, M.D., assistant professor in the WVU Department of Orthopaedics. Through pilot grant funding from the West Virginia Clinical and Translational Science Institute, patients in Dr. Watkins’ clinic are being enrolled in a human study of GPSM3 gene variations and their role in arthritis.

“The ultimate goal here is to translate our research into new therapies to help West Virginians,” Siderovski said. “West Virginia ranks among the top 12 states with the highest percentages of adults with arthritis. We need to do what we can to reverse that trend.”

The WHIM study was funded with support from NIH grants R03AR059286, K01AI091863 and K08AI070684 and an NCTraCS pilot project via support from NIH CTSA UL1TR000083.

The GPSM3 study was funded with support from NIH grants R01GM082892 and R03AR059286 and an NCTraCS pilot project via support from NIH CTSA UL1TR000083.

Pilot grant funding for continuing studies is disbursed through the WV IDeA-CTR NIH/NIGMS Award Number U54GM104942 in partnership with other WVCTSI member institutions (WVU, WVU-C/CAMC Institute and WVSOM).

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