Experimental Compound May Reduce Joint Inflammation in Rheumatoid Arthritis

Researchers using mice models have shown that the compound SR2211, which targets a nuclear receptor that is a key regulator of TH17 cells, significantly reduces joint inflammation and erosion.

A study published online by the journal Arthritis & Rheumatism reveals that scientists from the Florida campus of The Scripps Research Institute (TSRI) have created an experimental compound, known as SR2211, that, in animal models of rheumatoid arthritis, significantly reduced joint inflammation.

SR2211 targets the nuclear receptor RORγ, an important regulator of the white blood cell TH17. The TH17 cell controls production of the inflammatory cytokine IL17. Previous studies conducted by TSRI showed that SR2211 successfully suppressed IL17. The research team was also able to demonstrate that SR2211 blocked proinflammatory cytokine expression in LPS stimulated RAW264.7 cells.

The previous studies allowed the researchers to administer collagen-induced arthritis mice with the experimental compound SR2211 and evaluate its ability to reduce joint inflammation. SR2211 was given to the mice twice daily for 15 days. Within the first eight to ten days of treatment, virtually all symptoms of rheumatoid arthritis in the mice were blocked, and they showed reduced joint inflammation. The compound also reduced bone and cartilage erosion compared to animals that did not receive the treatment.

In a news release from The Scripps Research Institute, Patrick R. Griffin, PhD, chair of the TSRI Department of Molecular Therapeutics, said “This compound, and its precursors, showed the ability to block the release of specific inflammatory mediators from TH17 cells in culture, so we were confident that SR2211 would demonstrate good efficacy in rodent models of autoimmune disease.”

Griffin also noted that by demonstrating that “repressing the activity of the RORγ receptor alone works to reduce joint erosion and inflammation,” this study has identified “an alternative mechanism of action that can provide doctors with additional treatment options for patients who do not respond well or cannot tolerate current therapies.”