More MS news articles for Oct 2001

Proteins May Yield New Therapies for Bowel Disease

Monday October 22 5:24 PM ET
By Amy Norton

NEW YORK (Reuters Health) - Research into the immune system's inflammatory proteins has uncovered two new potential ways to fight inflammatory bowel disease (IBD).

In one study, investigators found that blocking an enzyme that regulates certain inflammatory proteins prevented intestinal inflammation in mice. A second research team garnered similar results when they blocked another protein that helps mediate inflammation.

The findings suggest two new targets for drugs to fight IBD, according to the researchers. And in one case, such drugs are already under study.

IBD is a general term for diseases that cause chronic inflammation in the digestive system, with ulcerative colitis and Crohn's disease being the two major types. Ulcerative colitis is marked by inflammation in the lining of the colon and rectum, and Crohn's typically occurs in the small intestine, although it can affect any part of the digestive system. Symptoms of both include diarrhea, abdominal pain, weight loss and bleeding. No medication can cure the disorders.

While the exact cause of Crohn's and colitis is unclear, scientists believe that an abnormal immune response causes the chronic inflammation that marks the disorders. So some of the drugs used to control them target the immune system. For example, a relatively new drug for moderate to severe Crohn's disease called infliximab suppresses the inflammatory protein tumor necrosis factor (TNF). But more treatments are needed, as different patients have different responses to existing drugs.

In one of the new studies, researchers at the University of Colorado Health Sciences Center in Denver found that blocking an enzyme called interleukin-1-beta-converting enzyme (ICE) prevented mice from developing chronic colitis. In contrast, mice with normally functioning ICE showed colon abnormalities, lost weight and had bleeding and diarrhea.

The findings were published Monday in the online early edition of the Proceedings of the National Academy of Sciences (news - web sites).

ICE inhibitors are now in clinical trials for rheumatoid arthritis, another inflammatory disease marked by an abnormal immune response. ICE inhibition may also offer a new treatment for IBD, Britta Siegmund, the study's lead author, told Reuters Health.

She noted that ICE inhibitors could have an advantage over anti-TNF drugs in that they can be given orally.

In the other study, researchers led by Ype P. de Jong of Beth Israel Deaconess Medical Center in Boston, Massachusetts, looked at an inflammatory protein called macrophage-migration inhibitory factor (MIF).

They found, similarly, that mice lacking MIF failed to develop chronic colitis. Moreover, they discovered that treating affected mice with anti-MIF therapy suppressed the disease.

And, hinting at what the finding could mean for humans, the researchers also found that MIF was elevated in the blood of a group of Crohn's disease patients.

Taken together, the study authors conclude, these findings suggest that ``intervention in MIF signalling could form a future target for the treatment of Crohn's disease.''

Their findings were published Monday in the online advance edition of Nature Immunology.

SOURCE: Proceedings of the National Academy of Sciences Early Edition 2001;10.1073; Nature Immunology online 22 October 2001;10.1038.

Copyright © 2001 Reuters Limited