Researchers Discovery Of Two Subtypes Of Crohn’s Disease Helps Doctors To Find The Best Therapeutic Course For Each Patient

Crohn's disease is known to be notoriously difficult to treat as there is no current cure for this disease, although there are treatments that can help control the disease by reducing the number of times patient experiences recurrences. Research conducted by University of North Carolina School of Medicine has discovered two subtypes of the disease - with different gene expressions and clinical features - that may reveal why such variations in disease progression surface between patients.

The discovery of two classes of Crohn's has implications for scientists to deliver more targeted treatments. This gives hope to doctors to find the best therapeutic course to each patient quickly and efficiently as possible.

What is Crohn's Disease?

Crohn's disease - a long-term condition that causes inflammation to the lining of the digestive system - affects almost 1 million people in the United States. While there is no cure for Crohn's, treatment with anti-inflammatory drugs and immune system suppressors can help improve symptoms.

The study findings were published in the journal Gut.

 "The one-treatment-fits-all approach doesn't seem to be working for Crohn's patients," says co-senior study author Dr. Shehzad Z. Sheikh, Ph.D., assistant professor in University of North Carolina's (UNC) departments of medicine and genetics.

"It's plausible that this is because only a subset of patients has the type of disease that responds to standard therapy, whereas, for the rest of the patients, we're really not hitting the right targets," he adds.

How do they do it?

The research team analyzed the colon tissue samples that looked healthy and non-inflamed in 21 Crohn's patients who had undergone surgery. They then mapped levels of gene expression patterns amongst the samples, finding that there were two distinct groups. They saw an even greater difference at the molecular level between these two subsets of the Crohn's samples - the healthy tissue from Crohn's patients and the inflamed samples from Crohn's patients.

Co-first author Jeremy Simon, Ph.D., a research assistant professor in UNC's department of genetics, notes that how the two disease subtypes differed was surprising.

In addition to analyzing gene expression in the sampled tissue, Sheikh and colleagues observed indicators of the epigenetic state of the DNA tissue that can permit or repress nearby gene activity. The team saw a distinction between the two Crohn's subtypes in the results that suggest the differences in gene expression emerge from variations in the core programming of the affected cells.

The team examined data from 201 children who had recently been diagnosed with Crohn's and had not yet been treated. While the tissue samples in the data were from the ileum, the same colon-like and ileum-like disease classes were observed.

"This suggests that these molecular programs or baseline genomic signatures of Crohn's subtypes exist independently of patients' ages or treatment histories," says Sheikh. He also points out that the two signatures are linked to different patterns of clinical illness.

In future work, the research team aims to develop a diagnostic test for use on tissue or blood samples were taken from routine colonoscopies. By identifying which Crohn's subtype a patient has, healthcare providers can determine the best therapy for treatment.

"We hope one day to be able to test Crohn's patients for the subtype of the disease they have, and thus determine which treatment should work best. The idea is to find the best therapeutic course for each patient as quickly and efficiently as possible."

Dr. Shehzad Z. Sheikh, Ph.D.