Every day, scientists work toward the advancement of rheumatoid arthritis (RA)treatment. And Dr. C. Michael Stein has made an exciting new discovery that could help these advancements along and predict how specific treatments will work.
Dr. Stein is looking at small molecules that have the potential to cause big problems. His 5-year Arthritis Foundation-funded project, “Extracellular small RNAs in rheumatoid arthritis,” is looking at how small molecules of ribonucleic acid (RNA) in the blood may be markers for different diseases.
“Our bodies make RNA as a genetic messenger that tells cells which proteins to make,” Dr. Stein explained. “Very small pieces of RNA found in the bloodstream are too small to code for proteins. [Scientists] thought these small RNAs were just junk. Recently, scientists have learned that these small RNA molecules are actually important regulators of many biological processes.”
“Recent information also shows that the type and amount of different small RNAs is different in various diseases,” Dr. Stein continued. “In other words, they could provide a ‘fingerprint’ that identifies a particular disease or even a particular complication of a disease.”
Dr. Stein and his team are looking at the small RNAs found in patients with RA. They would like to see if some small RNAs are associated with more active RA. For the first (pilot) part of this study, which began in early 2016, the team looked at the small RNA profiles of 12 RA patients and compared them to those found in 12 lupus (SLE) patients, as well as 12 healthy people (controls). They found differences in the small RNA profiles of each group. They also discovered the small RNAs were linked to disease-related pathways.
The results were encouraging, so this year the team will continue to look at small RNA profiles from additional RA and control patients. By 2019, Dr. Stein and his team plan to look at RA patients starting new treatments to see if drug response changes the small RNA profiles. Big factors in the conception of the study and its rapid progress have been the contributions of his co-investigators Dr. Michelle Ormseth, a rheumatologist studying small RNAs, Dr. Kasey Vickers, one of the leading experts in the biology of small RNAs, and a talented bioinformatics group.
“Small RNAs are not only markers, but they are also responsible for mediating some of the effects of diseases and there is the possibility that new treatments for illnesses could be developed by targeting small RNAs,” Dr. Stein explained. “We are interested in seeing if the small RNA profiles of particular patients with RA predict whether or not they will respond to a particular treatment.”
Scientists have recently discovered that about half of the small RNAs in the blood are non-human (from bacteria). “Nothing is known about these in RA. We want to find out if the profile of the non-human small RNAs is different in patients with RA and whether they might contribute to making RA better or worse,” Dr. Stein said.
Dr. Stein has been a supporter of the Arthritis Foundation for many years, taking part regularly in the Walk to Cure Arthritis. He describes his current project as high-risk with the potential of high rewards. “The Arthritis Foundation has been a champion of such studies that otherwise would be difficult to undertake,” he explained.
Dr. Stein said that his interest in RA stems from years of treating patients with the disease. “I have treated many patients with RA and appreciate the impact it has had on many people’s lives. There have been great advances, even since I started practicing in the 1980s. But I wish we could do more for our patients.”
Dr. Stein is the Dan May Professor of Medicine and Pharmacology, associate director of the Division of Clinical Pharmacology, and director of the fellowship program at Vanderbilt University School of Medicine. His work focuses on inflammation and cardiovascular disease (RA, SLE, and atherosclerosis).
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