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breakthroughs from the lab

POTENTIAL NEW THERAPY FOR CROHN’S, COLITIS IDENTIFIED

Originally published Oct 2019

BY TAMARA BHANDARI

More than 1 million people in the United States have inflammatory bowel disease, or IBD. This condition, which includes Crohn’s disease and ulcerative colitis, causes miserable episodes of abdominal pain, diarrhea and in severe cases, rectal bleeding, making life for those afflicted with the disease especially difficult.

ULCERATIVE COLITIS
HERE, THE CELLS THAT LINE THE GUT OF A PERSON WITH ULCERATIVE COLITIS ARE INFLAMED AND FILLED WITH A PROTEIN CALLED PAI-1 (SHOWN IN RED) THAT IS LINKED TO BLOOD CLOTTING. NUCLEI ARE SHOWN IN BLUE, AND OTHER INTESTINAL CELLS ARE MARKED IN GREEN. RESEARCHERS HAVE FOUND THAT BLOCKING THE PROTEIN POTENTIALLY COULD LEAD TO ALTERNATIVE THERAPIES FOR IBD.
Image by Gerard Kaiko, Washington University School of Medicine

Out-of-control inflammation is a marker for IBD, though it occurs in one part of the gastrointestinal tract with Crohn’s and another with ulcerative colitis. For many sufferers, the first line of treatment for IBD is general anti-inflammatory drugs such as corticosteroids. In more severe cases, physicians prescribe more potent immune suppressors, including TNF inhibitors that neutralize a specific immune protein. For some, these drugs are effective, but they may come with side effects: an increased risk of infection and cancer, for example. And others with IBD simply don’t experience much relief using standard methods of treatment.

All IBD sufferers may find the results of a recent study at Washington University School of Medicine especially welcome news. In a study of mice, researchers used a compound called MDI-2268—developed by Daniel Lawrence, PhD, of the University of Michigan—to block the activity of SERPINE-1, a gene that is switched on in areas of intestinal inflammation and damage. When this gene and its corresponding protein, PAI-1, are blocked, IBD symptoms diminish. As it turns out, SERPINE-1 and PAI-1 are especially active in people with severe IBD and in those whose symptoms don’t respond to TNF blockers.

“We found a unique target that’s not an inflammatory molecule, and yet blocking it reduces inflammation and signs of disease, at least in mice,” says Thaddeus Stappenbeck, MD, PhD, a scientist and professor of pathology and immunology at Washington University School of Medicine. “If further research bears out our findings, we think this target could be helpful to a greater number of patients.”

Originally published by Washington University School of Medicine at medicine.wustl.edu/news


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