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Antibiotic, gene therapy help treat angina

By KATRINA WOZNICKI, UPI Science News   |   Feb. 25, 2002 at 10:07 PM   |   Comments

WASHINGTON, Feb. 25 (UPI) -- Angina patients may have some new treatment options involving either gene therapy or doses of antibiotics, according to two new studies released Monday.

Angina, a common cardiovascular disorder affecting 7 million people in the United States, is severe chest pain caused by blood vessels too clogged to get oxygen-rich blood to the heart during physical activity. Current treatment involves either medication or, for more serious cases, rerouting the blood vessels -- perhaps with bypass surgery.

New treatments, however, are under development.

In one such study, researchers tested gene therapy to see if inserting genes to help create new blood vessels could effectively treat angina patients. Dr. Cindy Grines of William Beaumont Hospital in Royal Oak, Mich., studied 79 men and women, average age 60, with mild to moderate angina. The gene, a human growth factor gene called FGF4, was delivered via an inactive virus called Ad5 into 60 of the patients. The remaining 19 patients received a placebo. Among the gene therapy group, the patients on average had suffered from angina for 56 months, while the placebo group had endured angina for an average of 27 months.

All study participants underwent an exercise treadmill test prior to receiving treatment and then again after. At the beginning of the study, treadmill time was an average of 9.4 minutes for the placebo group and 9 minutes for the gene therapy group. After four weeks of treatment, exercise time for the placebo group only extended by 0.7 minutes, but the gene therapy group lengthened their exercise time by an average of 1.3 minutes. Even the 50 sickest patients of the group that received gene therapy improved their exercise time by 1.6 minutes compared to 0.6 minutes among the most severe cases in the placebo group.

The gene therapy essentially worked like jumper cables to jumpstart new blood vessel growth. This in turn improved blood flow during exercise, explained cardiologist Dr. Robert Engler, a consultant to Collateral Therapeutics -- the company that developed Ad5-FGF4. Engler is professor emeritus of medicine at the University of California at San Diego.

"I was pleasantly surprised by the results of this trial," Engler told United Press International. "We didn't expect to find any significant effects." He added, "I think there's tremendous promise for gene therapy to become part of the care for patients with coronary heart disease."

Engler said the U.S. Food and Drug Administration is also interested in this approach and a multi-center study across the U.S. and Europe is now being put together.

In a second study, researchers found blood flow could improve after antibiotic treatment among angina patients infected with Chlamydia pneumoniae.

Co-researcher Dr. Juan Carlos Kaski, a professor of cardiovascular science at St. George's Hospital Medical School, London, England, and colleagues studied 40 men, average age 55, who were randomly assigned to receive for five weeks either azithromycin, a common antibiotic used to treat Chlamydia pneumoniae infection, or a placebo.

To determine azithromycin's effectiveness, researchers measured what they called flow-mediated dilation of the brachial artery, how the blood flowed through the arm. After treatment, blood flow improved among the antibiotic group to a baseline of 4.78 percent, up from 2.66 percent. The placebo group showed no improvement; their baseline of 3.11 percent prior to treatment remained stagnant at 3.09 percent five weeks later.

Azithromycin also reduced blood levels of two markers that indicate endothelial dysfunction. Damage to the endothelium, a delicate lining inside the blood vessel, can lead to plaque buildup, which can then contribute to angina. Bacterial infections are believed to cause inflammation of the endothelium.

Both studies were published in the February 26 issue of Circulation, a journal of the American Heart Association.

"This is mainly a study that has identified that treatment with antibiotics improved the function of the artery," Kaski told UPI.

For many years, scientists questioned the role bacterial infections, particularly Chlamydia pneumonaie, play in cardiovascular disease.

"The question was, is this (infection) an innocent bystander or a culprit," Kaski said. Although the antibiotic worked, "the mechanism by how the antibiotic was effective was not very clear," he said.

Dr. David A. Meyerson, a cardiologist at Johns Hopkins Medical Center in Baltimore and a spokesman for the American Heart Association, said it's "too soon to recommend use of antibiotics to either treat or prevent heart disease," and it's unclear how the antibiotic is producing this effect.

On the issue of gene therapy, however, Meyerson said this holds a great deal of promise.

"This is truly exciting research," Meyerson said. "Currently, we have no adequate therapy for those patients with disabling angina already on maximum medications and whose anatomy does not permit angioplasty or bypass surgery. Ultimately, we would hope to use similar techniques to prevent heart attacks and stroke."

© 2002 United Press International, Inc. All Rights Reserved. Any reproduction, republication, redistribution and/or modification of any UPI content is expressly prohibited without UPI's prior written consent.
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