Personalizing Crohn’s disease therapies with microRNA as indicator

Crohn’s disease is an inflammatory bowel disease that involves lifelong management. Because disease development and potential complications vary among patients, it’s hard for physicians to determine a prognosis for each patient or to devise the best management plan accordingly. But a University of North Carolina-led team of researchers hopes its new findings in the role of a microRNA could point the way to personalizing treatment for this chronic disorder.

According to the team’s recent study published in the Journal of Clinical Investigation, microRNA-31 could offer the clue as to which Crohn’s patients are at higher risk of developing serious complications that need surgery.

The researchers performed small RNA-sequencing on colon tissues from both adults and children with or without Crohn’s. As it turned out, adults with low colonic micronRNA-31 expression at the time of surgery was associated with worse disease outcomes, requiring an end ileostomy and later recurrence of disease. Children with that feature were also linked to future development of strictures that required surgery.

To validate their findings, co-senior author Shehzad Sheikh, M.D., Ph.D., and colleagues used Crohn’s patients’ tissues to build “mini-guts,” also known as organoids, that physiologically resemble the human intestine. Because they preserve the original tissue’s molecular defects, the system “can serve as a personalized testing platform to screen therapeutic agents before administering them to the patient,” Sheikh said in a statement.

Scientists have been looking to mini-organs to assist in medical research. In 2014, researchers at Cincinnati Children’s Hospital reported to have grown healthy human intestinal organoids from induced pluripotent stem cells that could herald regenerative therapy to treat gastrointestinal diseases such as Crohn’s. A team from the hospital has also successfully built both the hormone-producing region and the corpus/fundus region of the stomach as potential models to study human gastric diseases.

Preserving tissue in organoids could result in heavily degraded mRNA, the study’s first author Benjamin Keith explained. But the team managed to overcome that with their system, which means it could be used to study more patient samples to further validate microRNA-31 and other microRNAs as markers to predict Crohn’s clinical outcome, he said.

Co-senior author Terry Furey, Ph.D., compared the UNC study’s potential in Crohn’s with cancer, where different molecular markers have been used to classify disease subtypes and hence to determine progression and best treatment options.

“Our long-term goal, extending the work in this study, is to uncover molecular subtypes of Crohn's disease to not only increase our understanding of the root causes of the disease and the vast clinical heterogeneity, but also to more strategically use current therapies and provide the basis for new therapies that specifically target these subtypes,” he said.