CROHN'S DISEASE: A new marker to better target treatment



 Crohn's disease (CD), a chronic inflammatory disease of the intestinal tract, has been steadily increasing for the past 50 years. While the condition brings together, experts say, a set of related but slightly different disorders, pinpointing the disease subtype accurately has remained a challenge. This team from Cornell University (New York) describes in the journal JCI Insight, the discovery of a unique miR-31 molecule, the levels of which make it possible to predict the “subtype of the patient”. An essential marker to opt for the right treatment decision, in particular in favor of surgical intervention or not.


In Crohn's disease, patients with subtype 1, unlike subtype 2, often respond poorly to medication and develop strictures or extreme narrowing of the intestinal tract, requiring surgery. The identified microRNA-31 or miR-31 marker will be useful in allowing clinicians to predict whether or not the patient should undergo preventive surgery before their condition worsens.

 

miR-31, predictor and factor of the disease: the researchers used state-of-the-art genomic techniques to track the abundance of different molecules in the colon tissues of more than 150 patients, children and adults. MicroRNAs control the degree of activation of a target gene. They work like negative switches: the greater the abundance of a microRNA, the more the target gene will be deleted. These genomic sequencing data allowed the researchers to discover miR-31, a predictive indicator of clinical outcomes, but also a key agent in the development of the disease.

 

An intestinal organoid to test therapeutic agents: During this work, Cornell researchers, together with their colleagues at the University of North Carolina, developed a state-of-the-art artificial intestine, called an intestinal organoid, which allowed them to culture samples of human biopsy while retaining the basic physiology that exists in humans. This innovative system can be used as a personalized test platform to test therapeutic agents before administering them to patients.

It's not personalized medicine yet, but this marker can lead to better clinical trial designs, says lead author Dr. Praveen Sethupathy, professor of biomedical sciences at Cornell's College. Research is already planned to explore what exactly miR-31 does and what role it plays in the integrity of the intestinal epithelium.

 

"  The long-term goal is to better understand at the molecular level why the disease is so different in its presentation among patients, and to use this knowledge to develop better targeted and more effective therapies  ."