Mechanisms of action studies of WBI-4002, a novel drug candidate promoting epithelial integrity

The cells lining our tissue surfaces in contact with the environment are called epithelial cells. To create a barrier epithelial cells are tightly connected to each other and are sometimes stacked upon each other, like on our skin. In the intestines the epithelium is only one cell thick in order to digest and absorb food. The result is that the "tightness" can be modified by events in the host or from products arriving in the lumen. These changes in "tightness" or integrity occur during diseases like Celiac disease or Crohn's disease and ulcerative colitis. While we understand the molecules involved in epithelial integrity we don't have many products that can improve it when we may need to, but we have some clues from our the food. Certain plants in our diet are thought to have anti-inflammatory and anti-oxidant properties (blueberries, for example). As scientists worked to purify the active plant products "polyphenol stilbenes" were discovered to have health benefits. Welichem Biotech Inc. (Burnaby, BC) has developed a drug in this class they call WBI-4002. WBI-4002 is a trans-hydroxystilbene. They have learned that the drug binds a molecule on the surface of cells called the aryl hydrocarbon receptor (AhR). The AhR is present on many types of cells including on epithelial cells. Other researchers showed that when the AhR binds compatible molecules it can improve the integrity of the epithelium. Welichem Biotech Inc. wants to know if their drug can also modify the integrity of epithelium. The Company contacted Dr. Stadnyk, who is an expert on the intestinal epithelium. Dr. Stadnyk will apply WBI-4002 to intestinal epithelial cells, from humans and mice, in petri dishes, and measure any effects on integrity. He will examine the molecules that make up the bonds between cells to figure out what changes when WBI0-4002 is applied. If the drug works to improve epithelial integrity it may be a good candidate for treating inflammatory diseases of the intestines.