Researchers at BC Children’s Hospital (BCCH) and the University of British Columbia have found a new sub-type of inflammatory bowel disease (IBD) that can be treated with existing drugs that target the body’s inflammatory response. This discovery may help children who have been diagnosed with Crohn’s disease but aren’t responding to current treatments.
“This research opens up a whole new class of drugs as a potential treatment for patients with IBD,” says BCCH investigator and UBC Associate Professor, Dr. Laura Sly, lead author of the study in Gastroenterology. “These therapies are already in use for children with other conditions, so our findings have the potential to be translated rapidly.”
Inflammatory bowel disease (IBD) is an umbrella term for conditions affecting the colon and small intestine, including Crohn’s disease and ulcerative colitis. Symptoms of IBD include painful abdominal cramps, diarrhea and vomiting. IBD occurs when the body’s immune system mistakenly triggers inflammation in the digestive tract. Inflammation is part of the body’s normal response to illness and injury, but in conditions like IBD it can cause severe damage to healthy tissue.
In previous research, Dr. Sly and her colleagues showed that genetic variations that cause low levels of an enzyme called SHIP can contribute to the inflammation seen in IBD. In this study, they examined mice with low levels of SHIP and intestinal inflammation to pinpoint the immune process behind their condition.
They found a process mediated by a protein called cytokine lL1 beta amplifies inflammation leading to a condition that causes symptoms like those seen in Crohn’s disease. Researchers also studied intestinal cells collected from children with Crohn’s disease and found low levels of SHIP and high levels of IL-beta. This research shows that in some children diagnosed with Crohn’s, overactive IL1 beta may be contributing to their symptoms. These children may respond to existing drugs that block IL1 beta, which are already in use for children with other immune conditions.
“Only recently, scientists and clinicians have begun to understand both Crohn’s disease and ulcerative colitis are also umbrella terms that probably encompass many different sub-types of disease with unique causes,” says Dr. Sly. “By learning more about these sub-types, we can provide more effective, personalized treatments to children with IBD.”
This research holds particular promise for the 10 to 20 per cent of IBD patients who don’t respond to any of the currently available medications. IBD patients who can’t be treated with drugs may have to undergo surgery to remove their colons. Children who have this surgery must use a colostomy bag for the rest of their lives and may suffer from nutrient malabsorption and other complications.
“The surgical treatments for IBD are extreme and life-changing, especially for children,” says Dr. Sly. “We really want to provide better alternatives for these kids and we hope this research will open new treatment options for children who aren’t responding to other therapies.”
In the next phase of this research, scientists will examine tissue samples from patients who aren’t responding to current treatments for IBD to see if they might be candidates for drugs that block IL1 beta. Clinicians can then move towards treating these patients with IL1 beta blocking medications and evaluating if the new therapy is effective.
Ngoh EN, Weisser SB, Lo Y, Kozicky LK, Jen R, Brugger HK, Menzies SC, McLarren KW, Nackiewicz D, van Rooijen N, Jacobson K, Ehses JA, Turvey SE, Sly LM. Activity of SHIP, Which Prevents Expression of Interleukin 1β, Is Reduced in Patients With Crohn's Disease. Gastroenterology. 2016 Feb; 150(2):465-76. doi: 10.1053/j.gastro.2015.09.049. Epub 2015 Oct 19. PMID: 26481854
This study was supported by the Canadian Institutes of Health Research (CIHR). The researchers are supported by BC Children’s Hospital Foundation, the CH.I.L.D. Foundation, CIHR, Crohn’s and Colitis Canada, the Canadian Association of Gastroenterology, MITACS, the University of British Columbia, and the Michael Smith Foundation for Health Research.
- Dr. Laura Sly: Scientist, BC Children's Hospital; Assistant Professor, UBC Department of Pediatrics
- Dr. Kevan Jacobson: Investigator, BC Children's Hospital; Head, Division of Gastroenterology, Hepatology and Nutrition, UBC Department of Pediatrics; Associate Member, UBC Department of Physiology
- Dr. Stuart Turvey: Investigator, Director, Clinical Research, and Pediatric Immunologist, BC Children’s Hospital; Aubrey J. Tingle Professor of Pediatric Immunology, UBC Department of Pediatrics
- Dr. Eyler Ngoh: UBC Doctoral Student supervised by Dr. Sly
- Dr. Shelley Weisser: UBC Doctoral Student supervised by Dr. Sly at the time the research was conducted
- Young Lo: UBC Masters Student supervised by Dr. Sly
- Lisa Kozicky: UBC Masters Student supervised by Dr. Sly
- Roger Jen: Research Technologist, Sly lab, BC Children’s Hospital
- Hayley Brugger: Research Technologist, Sly lab, BC Children’s Hospital
- Susan Menzies: Research Technologist, Sly lab, BC Children’s Hospital
- Dr. Keith McLarren: Research Associate, BC Children's Hospital