An experimental drug compound could pave the way for a new kind of rheumatoid arthritis treatment with fewer side effects.
As painful as rheumatoid arthritis (RA) can be for patients, sometimes treatment can be just as unpleasant. Many drugs for the inflammatory autoimmune disease come with a host of side effects, including pneumonia, infection, and in some cases, hair loss.
Now scientists from the Florida campus of The Scripps Research Institute (TSRI) are using an experimental drug compound to tackle both the symptoms of RA and the side effects of common treatments. The research, published last week in the journal
The compound, known as SR2211, prevents the symptoms of RA by blocking the release of inflammatory cytokines, which are chemical messengers that regulate processes in the immune system. Not all cytokines are inflammatory; it’s the imbalance of pro- and anti-inflammatory cytokines that leads to inflammation and joint damage experienced by RA patients.
The key action of the compound is to suppress the nuclear receptor RORy, which regulates the TH17 blood cells that are responsible for producing cytokines. In the study, mice who had been injected with SR2211 showed fewer arthritis symptoms within eight to ten days, as well as significantly reduced bone and cartilage erosion compared to mice who hadn’t received the treatment.
Many current RA treatments are associated with an increased risk of infection and pneumonia. This is because they suppress the entire immune system, which can take a dangerous toll on the patient if he or she is treated for an extended period of time.
“Most commonly used therapeutics are ‘biologics,’ which have been optimized for long half-life in blood (up to several weeks), so if you get an infection it could be fatal,” explains study author Dr. Patrick R. Griffin, chair of the TSRI Department of Molecular Therapeutics.
But with further development, SR2211 could make the process less dangerous for patients, and could also produce better results in shorter periods of time.
“A once-a-day small molecule pill will be cleared [from the body] within 24 hours, and the drug can be stopped at any sign of infection,” Griffin says. “Also, the current therapies target one specific pro-inflammatory molecule, whereas [ROR suppressing drugs like SR2211] target a specific class of immune cells.”
The drug compound has the potential to treat a host of autoimmune diseases. As the study notes, TH17 cells have been linked to many autoimmune diseases, including multiple sclerosis, inflammatory bowel diseases, and lupus.
“Many pharma companies are working on targeting RORs,” Griffin says. “Our paper shows that they should consider testing their compounds in RA models so that if a compound progresses to the clinical [stage] they can test it in RA patients.”