miR-31 Can Help Target Treatments for Crohn's Patients

Crohn's disease (CD), a chronic inflammatory disease of the intestinal tract, has become a global disease, with rates increasing steadily over the last 50 years. Experts have long suspected that CD probably represents a set of related but slightly different disorders, but it has not yet been possible to accurately predict the subtype of MC that a patient is likely to develop.

Researchers at Cornell University and the University of North Carolina have identified a unique molecule – microRNA-31 (miR-31) – whose levels predict whether a patient is a subtype 1 or 2.

This is important because subtype 1 patients, unlike subtype 2, often do not respond well to drugs and develop stenoses – an extreme narrowing of the intestinal tract, requiring surgery once developed. Markers such as miR-31 may be useful in the future for clinicians to predict whether a patient should undergo preventative surgery before the condition worsens.

"We are not at the forefront of personalized medicine in this area, but we think at least that this can lead to better clinical trial designs," said Praveen Sethupathy, associate professor in the Department of Biomedical Sciences of Cornell College of Veterinary Medicine and co-lead author of the study, with Terrence Furey, associate professor of genetics, and Dr. Shehzad Sheikh, associate professor of medicine, both at the UNC.

According to Professor Sethupathy, clinical trials have generally grouped all patients in the trial of a new treatment for CD, leading to inconsistent results from one group to another. By using miR-31, researchers could eventually separate people with CD subtypes to more accurately determine whether a particular drug works for one subtype and not for the other.

In this study, the researchers also used an ultramodern artificial intestine called the intestinal organoid, which allowed them to grow human biopsy samples while maintaining the basic physiology that exists in humans. "This innovative system can serve as a customized testing platform for screening therapeutic agents before they are administered to patients," said Dr. Sheikh.

Researchers have also used advanced genomic techniques to track the abundance of different molecules in colon tissue from more than 150 pediatric and adult patients. MicroRNAs control the degree of activation of a target gene. They work as negative dials – the greater the abundance of a microRNA is large, the more a target gene will be deleted. Genomic sequencing technology data enabled researchers to discover miR-31.

"Our study suggests that miR-31 could not only be a predictor of clinical outcomes, but also that it may play an important role in the management of the disease," said Professor Sethupathy.

Future work will explore exactly what miR-31 does and what role it could play in the integrity of the intestinal epithelium. "Our long-term goal, by extending the work of this study, is to better understand at the molecular level why CD is so different in its presentation among patients and to use that knowledge to develop more effective therapies," said Furey.

The study was published in the journal JCI Insight.