Inhibiting Serine Synthesis as a Novel Treatment for Intestinal Fibrosis.

Patients with Inflammatory Bowel Disease (IBD) can experience many years of inflammation and remission in the gastrointestinal tract. As a result, the intestines can undergo a structural change known as fibrosis, which narrows the inside. This narrowing is a major, and sometimes life-threatening, health issue for patients because it can block the passage of digested food and stool. Unfortunately, the only treatment for this condition consists of invasive surgical procedures to either widen the opening or remove the affected areas of the intestine. Therefore, there is an urgent need to develop less invasive therapies such as drug-based treatments. Preliminary studies carried out in our laboratory have pointed to a potential role for the molecule serine, an amino acid, in the development of intestinal fibrosis. For example, we have found that serine is produced in areas of fibrosis in the intestines of IBD patients and in our mouse model of intestinal fibrosis, suggesting that it may play a role in the development of this condition. The work proposed in this application will determine if in fact serine is largely responsible for intestinal fibrosis and establish methods to limit its production and thus prevent fibrosis development. Carrying out the proposed work can lead to the development of novel treatments for intestinal fibrosis and significantly improve the lives of patients with IBD.