US Pharm. 2018;43(12):4.
Crohn’s disease (CD), a form of chronic inflammatory bowel disease, is a common gastrointestinal disease with increasing incidence worldwide. Scientists long theorized that CD is a group of similar but slightly different disorders, yet predicting which disease subtype a patient is likely to develop remained a challenge.
In a study published in October in JCI Insight, researchers from Cornell University and the University of North Carolina (UNC) report that they have identified a molecule called microRNA-31 (miR-31) with potential importance to Crohn’s treatment. Levels of the molecule, they say, portend whether a patient has Crohn’s disease subtype 1 or subtype 2. This is impactful, because persons with Crohn’s subtype 1 frequently do not respond positively to treatment, even developing strictures—narrowing of the gut tube that necessitates surgery. Markers like miR-31 could also be useful for predicting whether a patient should pursue pre-emptive surgery before the condition worsens.
“We are not at the point at which we are able to perform personalized medicine on this, but at the very least we think it can lead to better clinical trial designs,” said Praveen Sethupathy, associate professor in the Department of Biomedical Sciences at Cornell’s College of Veterinary Medicine and a senior coauthor of the study, along with Terrence Furey, associate professor of genetics, and Dr. Shehzad Sheikh, associate professor of medicine, both at UNC.
For the most part, clinical trials group all patients when testing a new CD therapy, which leads to inconsistent results across the subjects, Sethupathy explained. Employing miR-31, researchers might be able to separate individuals with CD into subtypes so that they can more accurately determine if a specific medication is more effective against one CD subtype.
In the study, the investigators used a state-of-the-art artificial gut, called an intestinal organoid, that permitted them to culture human biopsy samples while retaining their basic physiology. “This innovative system can serve as a personalized testing platform to screen therapeutic agents before administering them to patients,” Sheikh said.
The research team also used state-of-the-art genomic methods to track the abundance of different molecules in the colon tissue of patients with CD. MicroRNAs function as negative dials: the greater amount of a microRNA, the more a target gene will be suppressed. This sequencing data allowed them to make their miR-31 discovery. “Our study hints that it’s not only that miR-31 could be a predictive indicator of clinical outcome but also that it could be functionally relevant in driving the disease,” Sethupathy said.
Keep abreast of the latest CD treatment guidelines from the American College of Gastroenterology in this issue’s article, “Crohn’s Disease Treatment Update,” by Priyam Mithawala, PharmD.
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