Discovering Novel Treatments

Dr. Theodore Steiner  | University of British Columbia
Research: Exploring the therapeutic potential of type-1 regulatory T cells in Crohn's ileitis
Date: 2020-2021
Amount: $50,000

Treatments for Crohn’s disease have improved during the past 20 years, but many patients unfortunately still experience symptoms or complications. To advance treatment options, Dr. Steiner and his co-principal investigators Dr. Laura Sly and Dr. Megan Levings are working to enhance a potential new treatment for Crohn’s disease by using type-1 regulatory (Tr1) cells – cells that play a special role in suppressing inflammation. These researchers have discovered that these cells have unique effects on the gut that may benefit people with Crohn’s disease.

The research team has identified that mice develop a disease similar to Crohn’s disease due to the absence of an immune protein, SHIP1. They discovered that putting Tr1 cells into SHIP-deficient mice protects them from developing the disease. People with Crohn’s disease also lack the SHIP1 immune protein, making mice a good animal model to study. This Crohn’s and Colitis Canada funded research project will support larger experiments with animal models to confirm this effect, determine how Tr1 cells are protective, and optimize ways to grow these cells to improve how they work. If the experiments are successful, the researchers will build a larger project to complete preclinical testing with animal models to lay the groundwork for Tr1 therapy in people.

Dr. François Boudreau  | Université de Sherbrooke
Research: Repurposing drugs to target HNF4A during IBD
Date: 2020-2023
Amount: $50,000

The intestinal epithelium is a single layer of cells that forms a barrier that protects the host and its immune system from threatening bacteria. Defects in this barrier affect the progression of inflammatory bowel disease (IBD). By identifying therapeutic molecules that enhance the epithelial barrier and limit inflammation, we can halt the progression of IBD. Dr. Boudreau and his team have identified the protein HNF4A is a central epithelial regulator that maintains the function of the intestinal epithelium and protects against susceptibility to IBD. This research project aims to identify drugs – already approved and deemed safe for human use – that reinforce the activity of HNF4A in maintaining the function of this barrier. The team is taking a unique approach as they are creating advanced epithelial cellular models and using an automated microscope system to screen the reinforcing activity of over 1,500 drugs in protecting against features of IBD. The project presents the opportunity to expedite preclinical testing of validated drugs examined in the study.

Dr. Dana Philpott  | University of Toronto
Research: The role of LRRK2 in the pathogenesis of Crohn’s disease
Date: 2020-2023
Amount: $375,000

Variants in a number of genes are associated with the development of Crohn’s disease. So far, only a handful of studies have examined the gene encoding Leucine-rich repeat kinase 2 (LRRK2) which has been linked to both Crohn’s disease and Parkinson’s disease. The LRRK2 gene variants in both diseases result in a similar dysfunctional protein. While the diseases are seemingly unrelated, the presence of shared genetic risk and co-incidence of Parkinson’s disease in people with inflammatory bowel disease (IBD) suggests common pathways are involved in their development.

Dr. Philpott and her team are examining how the LRRK2 variant in Crohn’s disease affects the ability of white blood cells to protect the body from infection. They observed white blood cells from engineered mice with defects in LRRK2 were unable to properly move to sites of infection and inflammation and fail to kill invading microbes. Thanks to Crohn’s and Colitis Canada, Dr. Philpott and her lab are examining how LRRK2 variants affect intestinal inflammation and if targeting LRRK2 activity with drugs in development to treat Parkinson’s disease can act as a potential treatment for Crohn’s disease.