For more than a decade, Calgarian Grant Silbernagel, 61, has lived with Crohn’s disease (CD), the same inflammatory bowel disease both his father and adult son struggle with.
Silbernagel says life with CD can be debilitating, but also calls it his “adventure.” In and out of remission many times, he’s tried several medications, including one that made his bones so weak that he suffered spinal compression fractures requiring surgery.
Silbernagel hopes two newly-funded research projects at the Cumming School of Medicine’s Snyder Institute for Chronic Diseases will change his life and those of all Canadians living with inflammatory bowel disease (IBD). The University of Calgary was recently awarded philanthropic gifts from The Leona M. and Harry B. Helmsley Charitable Trust, totalling nearly $2.6 million, to support this research.
Grant Silbernagel, who lives with Crohn’s disease, feels hopeful about new UCalgary research to reverse damage and better inform Crohn’s treatment. Photo courtesy Grant Silbernagel.
Molecular mystery
Dr. Cathy Lu, MD, and her research team are working to identify which CD patients will develop intestinal scar tissue, which causes narrowing and leads to blockages. Some CD patients become so ill they must be admitted to the hospital or require surgery.
In groundbreaking research, Dr. Lu, along with Dr. Simon Hirota, PhD, and Dr. Antoine DuFour, PhD, are working to pinpoint protein signatures — measurable signs within some of our bloodstream molecules — telling the intestinal walls of CD patients to grow scar tissue, causing them to narrow. It’s a first step to developing new precision medical treatments and preventive strategies for CD patients.
“For example, using a simple blood test rather than a colonoscopy or MRI scan — both of which are not always quickly available — will help detect if a narrowing is present before end-stage changes occur, helping us recommend surgery or medication changes, and leading to better outcomes and quality of life for patients,” says Dr. Lu.
Dr. Lu and her team plan to forge ahead with their new two-year investigation to gather, image and compare the protein signatures of CD patients with and without narrowed intestines, along with those of healthy patients. Participants will be recruited through UCalgary’s inflammatory bowel disease (IBD) clinics for the project, titled Quantitative Proteomic Profiling of Fibrostenotic Crohn’s Disease Patients.
Crohn’s disease-fighting immune cells
A second Snyder Institute study aims to enhance treatment and prolong remission for people living with CD. The investigation by Snyder Institute Director Dr. Derek McKay, PhD, and co-researcher Dr. Remo Panaccione, MD, will allow for future testing of a personalized cellular immunotherapy to treat CD.
This approach uses the body’s own immune system cells to treat illness. McKay and his team previously discovered that interleukin-4 activates macrophages (M(IL-4)) — a pro-healing type of white blood cell in the immune system — to reverse colitis in lab tests. They believe future custom cell therapies created from an IBD patient’s own M(IL-4) could reduce inflammation, improve healing, and extend disease remission, as an add-on to approved IBD drugs.
“This is not drug manipulation. It’s using a patient’s own cells to take on a task they’ve naturally evolved to do, then putting these cells back into the patient to reduce colon inflammation,” McKay says.
This kind of immunotherapy is a bold new approach for CD. The researchers plan to launch a clinical trial and recruit CD patients, both active and in remission, for the three-year study beginning April 2022. The study, titled Interleukin-4 Activated Macrophages (M(IL4)) for Personalized Cellular Immunotherapy to Treat IBD, will also help identify which patients will not respond to M(IL-4) immunotherapy, why it won’t work for them, and the markers in their macrophages that flag this.
“Going through my life and also seeing the problems my own child had, I would love to see this research lead to new diagnostics and treatment for all patients,” says Silbernagel.
Join us on January 10 for Virtual Mini-Medical School: Nutrition, IBS, and Fatty Liver Disease. Register for free at snyder.ucalgary.ca/series-seven.
