Precision Medicine Ulcerative Colitis Studies Assess Gene Expression, Prediction, and Better Understanding of Biological Pathways

One study illuminates the genes that may prove useful in predicting how ulcerative colitis will progress in children and teens; the other investigates poorly understood disease-relevant biological pathways

Gastroenterologists and other healthcare providers seeing increasing cases of inflammatory bowel disease (IBD), specifically moderate to severe ulcerative colitis, may be interested in recent research into the genetics that may influence the condition’s progression and severity.

As many know, ulcerative colitis (one of the two primary forms of IBD) affects the colon and causes bleeding and abdominal discomfort. The condition can worsen to the point of requiring major surgery. Although there have been numerous clinical trials for ulcerative colitis, its exact cause and best treatments are not fully understood. Pediatrics is an area of specialized study.

Improving Ulcerative Colitis Care for Teens

In an effort to better predict the severity of IBD, Stanford Medicine researchers used microfluidic technology to study disease progression and medication response. The researchers wanted to shed light on the unpredictable nature of the disease and the extent to which trial and error plays in treatment. If specialized testing could better predict the severity of IBD and response to treatment, that might enable better selection of treatment earlier in the disease process.

The related study, published in the Journal of Crohn’s and Colitis, explains how the Stanford team examined gene expression in over 400 samples of newly diagnosed ulcerative colitis pediatric patients. Importantly, the researchers associated the activity of two specific genes (IL13RA2 and RORC) with outcomes at the one-year mark. They concluded that the targeted assessment of gene expression could be predictive, and further studies are warranted, according to the paper.

Predicting progression of the disease is important because it could direct clinicians on which treatments to use, said physician scientist Michael Rosen, MD, in an interview for the Stanford Scope Blog. Rosen is a pediatric gastroenterologist at Stanford Children’s Health and the senior researcher of the project.

Probing Into Probability of Response to Ulcerative Colitis Treatment

Stanford Medicine pediatric gastroenterologist Michael Rosen, MD, patterns of gene activity, ulcerative colitis
Stanford Medicine pediatric gastroenterologist Michael Rosen, MD (above), studies patterns of gene activity in patients with ulcerative colitis. (Photo: Doug Peck via Scope Blog)

“A recent study showed that only about one-third of patients achieve long-term clinical remission on the traditional oral medication alone,” Rosen told Scope. “But for patients who don’t respond well to this class of drugs, trying this treatment prolongs getting their symptoms under control. It would be wonderful if we could identify these patients at the time of diagnosis, because then we could get an earlier start on therapies that are more likely to help them.”

Rosen’s team found that by combining information from gene expression with other clinical data, the researchers were able to predict which patients would require more advanced treatments.

“We found that when we combine patients’ gene-expression information and clinical measurements, such as their hemoglobin level, which measures anemia, as well as their symptom severity at diagnosis, we better predict who will need escalated therapy,” Rosen said, adding that the study results must be further validated. “This improves on our current method of identifying who needs more intense therapy, which requires waiting four weeks after diagnosis to see how a patient is doing.”

Rosen also explained that being able to predict how well a medication will work has tremendous value to both patients and clinicians. “Families may feel discouraged by the idea of trying a medicine with only a 30% to 40% chance of being effective. If we could say, ‘For your child, there is a 60% chance this will work,’ that would be huge. Alternatively, if we know that a patient has only a 10% chance of succeeding on a particular medication, we probably would try something different.”

Identifying New Mechanisms of Ulcerative Colitis

Understanding disease-relevant biological pathways is essential for developing effective precision medicine programs for people with ulcerative colitis and other IBD-related complications. To that end, a study out of the United Kingdom, published in Nature, suggests a new integrated systems genomics workflow for determining the functional role of disease-associated single nucleotide polymorphisms (SNPs) in the noncoding regions of the genome. SNPs are small genetic variations occurring within a DNA sequence.

Because coding SNPs comprise less than 10% of the total ulcerative colitis-associated SNPs, the researchers asserted that “functional annotation at the molecular and systems-level of the remaining 90% SNPs located in non-coding regions would expand the utility of these disease-associated SNPs,” according to the related Nature article.

The study finds researchers from the Quadram Institute, the Earlham Institute, the Norfolk and Norwich University Hospital, and University of East Anglia proposing using a systems-level approach to stratify patients, according to details of the article in Nature. Ultimately, this particular ulcerative colitis study implicated calcium regulation, wound healing, and the ability of cells to move.

“The workflow’s ability to identify cohorts of disease associated mutations and pathways isn’t limited to IBD; it has the potential for use in other complex disease including mental health, heart disease and autoimmune conditions,” co-lead study author Tamas Korcsmaros, PhD, of the Earlham Institute, said in a related Genetic Engineering and Biotechnology News article.

After passing additional scientific validation and rigor, these insights, should they stand true to the promise of precision medicine, will improve our understanding of patient-specific considerations relative to ulcerative colitis. In turn, the discoveries could accelerate more effective and timely therapy, earlier in the disease process. In the meantime, the ulcerative colitis studies will add to the body of knowledge toward developing precision medicine programs in gastroenterology.

—Caleb Williams

Related Information:

Targeted Assessment of Mucosal Immune Gene Expression Predicts Clinical Outcomes in Children with Ulcerative Colitis

Precision Medicine Predicts Best Ulcerative Colitis Care for Teens

A Systems Genomics Approach to Uncover Patient-Specific Pathogenic Pathways and Proteins in Ulcerative Colitis

Personalized Medicine Could Be Improved by New Precision Medicine Tool  

Michael Rosen, MD

Tamas Korcsmaros, PhD

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