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Treatment for colitis shows early success. (Intestinal Fortitude).

The cells that line the gastrointestinal tract, among other responsibilities, keep the immune system from reacting to bacteria and food in the gut. In people with ulcerative colitis, however, breaches in this epithelial cell layer bring immune cells into contact with the foreign material. The result is inflammation and ulcers in the colon and rectum.

A novel approach to therapy for the disease now shifts the priority from quelling the immune reaction to rebuilding the epithelial layer. In its first test in people, the treatment has yielded dramatic improvements, British scientists report in the July 24 New England Journal of Medicine. To refurbish the cell layer, the researchers gave patients massive doses of the human gut peptide called epidermal growth factor (EGF). The peptide had been produced in genetically engineered yeast.

Jeremy M.D. Nightingale of the Leicester Royal Infirmary in England and his colleagues randomly assigned 12 people with ulcerative colitis of the colon and rectum to receive, over 2 weeks, daily enemas containing EGF. Twelve other patients with similar disease received saline enemas as a placebo. People in both groups also got pills containing the anti-inflammatory drug mesalamine.

Ulcerative colitis, a recurring disease, is marked by gut pain, chronic diarrhea, blood in the stool, weight loss, and weakness.

Four weeks after the start of the trial, 10 of the 12 people getting EGF were free of most symptoms, but only 3 of the 12 people getting saline enemas were. After nearly 3 months, eight people in the EGF group but only one in the other group remained largely free of symptoms. Moreover, nine people in the placebo group but only four in the EGF group had developed serious symptoms that required treatment with steroids that suppress the immune system.

"This is one of the most exciting studies to come across my desk in years," says D. Brent Polk of Vanderbilt University Medical Center in Nashville. "This is a significant advance that suggests we can treat the epithelial injury as well as the immune response."

Writing in the journal carrying the new study, Richard J. Farrell of Harvard Medical School in Boston says that while the new findings are "impressive," they need to be confirmed in tests without mesalamine to sort out more precisely the benefits of EGF.

Polk suggests that researchers will next need to compare EGF treatment head-to-head against anti-inflammatory therapies, including steroids. While anti-inflammatory drugs offer some relief and give the epithelial layer a chance to heal in some patients, they have serious side effects. Steroids can cause high blood pressure, mood swings, insomnia, indigestion, and high blood sugar concentrations.

The current study will probably also spawn laboratory research to determine how EGF rebuilds the epithelial lining, Polk says.

Nightingale's team plans to follow the 24 patients to see whether cancer develops, even though animal studies suggest the peptide is safe.

If the benefits of EGF hold up, Nightingale says, he will push for a large-scale test of EGF in hundreds of patients.
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Author:Seppa, N.
Publication:Science News
Geographic Code:4EUUK
Date:Jul 26, 2003
Words:497
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