UVa Doctors Find New Target for Future Crohn’s Disease Therapy

Digestive specialists at the University of Virginia Health System have found that a protein called TL1A plays an important role in the development of inflammatory bowel disease, or IBD. Their findings may give researchers a new target for future therapies for Crohn’s disease, which affects about one million people in North America. The research, with colleagues at the Alexander Fleming Biomedical Sciences Research Center in Vari, Greece, is published in the May 12 online edition of Proceedings of the National Academy of Sciences (PNAS).

Crohn’s is a chronic inflammatory disease of the gastrointestinal tract. Doctors still don’t know what causes it and there is no cure. The symptoms of Crohn’s include abdominal pain, diarrhoea, weight loss, malnutrition and arthritis. It is a manageable disease, but people with severe Crohn’s usually have to be on special medication. TL1A is part of a family of proteins called cytokines that regulate cell growth and function during inflammation and the body’s immune response to disease. Already, the main treatment for people with Crohn’s is anti-TNF (tumor necrosis factor) therapy, including drugs such as Remicade. TNF is a cytokine also involved in inflammation. In lab experiments, UVa scientists led by Dr. Fabio Cominelli, chief of gastroenterology and hepatology at UVa’s Digestive Health Center of Excellence, were able to characterize the function of TL1A in mice with Crohn’s. Their results raise the possibility that blocking the pathway by which TL1A interacts with a receptor (called DR3) on intestinal cells could offer therapeutic opportunities for Crohn’s researchers and, hopefully soon, for patients as well. “We know that blocking TNF gives dramatic response in Crohn’s patients,” Cominelli said. “Our hope is that this therapy will be similarly effective in patients who do not respond to other therapies, or used in combination with anti-TNF, to suppress Crohn’s. This research has implications for developing novel drugs that are more effective and more specific, with less side-effects.” Cominelli said he and his team of researchers at UVa are making progress in unraveling the basic mechanism of Crohn’s in the cell. He called this finding “another step in understanding the cause of this disease.”(Source: Proceedings of the National Academy of Sciences: University of Virginia Health System: June 2006.)