Targeting the septin cytoskeleton as a novel mechanistic approach to therapy of fibrostenosing Crohn’s disease.

More than half of Crohn’s disease (CD) patients develop excessive scar tissue leading to intestinal blockage, ultimately requiring surgery with removal of parts of the bowel. This process can repeat itself, often resulting in multiple surgeries. There are many therapies that treat gut inflammation, but even when gut inflammation is controlled excessive scar tissue still forms. There is no therapy to prevent or treat intestinal scars. We therefore need to understand how to block scar tissue formation or promote its resolution. The main producers of scar tissue proteins, the myofibroblasts, are not targeted by current therapies. We believe that changes of the structural scaffold inside the myofibroblasts plays a critical role in making them produce scar proteins. We will test this by modulating the fibroblast scaffold in cell experiments and living organisms (mice). This has never been done before and is a novel approach to treatment of this disease complication.