Duke rheumatology researchers are examining the effects of microRNAs (miRNAs) on inflammatory diseases such as rheumatoid arthritis (RA) with the long-term goal of developing new therapeutic agents to treat RA and related autoimmune conditions.

Research involving cellular inflammatory responses has yielded several effective controls such as tumor necrosis factor (TNF) inhibitors in recent decades. Despite the progress, patients with RA, researchers say, still have limited ability to exercise and have an elevated risk for cardiometabolic disease.

Kim H. Huffman, MD, PhD, and Brian Andonian, MD, are leading the Division of Rheumatology and Immunology’s examination of the effects of miRNAs on cellular processes in the body that affect skeletal muscle and metabolism. Huffman says the project has been strengthed by a collaboration with Virginia Byers Kraus, MD, PhD, a leading rheumatology researcher, and Ching-Heng Chou, PhD, a molecular microbiologist. “As a team, we’ve been working diligently to better understand the ways in which miRNAs predict disease and healthy aging,” Huffman says.

Huffman and Andonian have launched a related project to examine skeletal muscle inflammation and its relationship to muscle function as part of their mechanobiology study, which may also offer insights into RA comorbidities.

“Despite the scientific progress in developing anti-inflammatory agents, we still see a high incidence of cardiovascular disease, general disability, and increased mortality among the population of patients with RA,” says Andonian, a Duke rheumatology fellow. “Based on these observations, it’s clear that current medications for inflammatory disease simply don’t do enough. We should be able to do more.”

Andonian cites several key highlights from the team’s initial research into miRNAs:

• miRNAs regulate post-transcriptional gene expression and protein synthesis.
• Altered miRNA expression is associated with multiple biologic processes, including cellular responses, inflammation, and metabolism.
• miRNAs are potential biomarkers and therapeutic targets in RA and other autoimmune diseases.

Researchers’ increasing ability to identify miRNAs in human tissues and tissue compartments have led to the findings that suggest miRNAs may be effective biomarkers with the potential to improve diagnosis and provide more targeted treatments to patients with autoimmune  inflammatory diseases.

“miRNAs perform many different tasks within the tissues and have many impacts across multiple pathways in the body,” Andonian says. “They cross membranes and have transport systems that allow them to get into different areas of cells.”