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Genetic Tests Reveal How Heart Drugs Work

Scientists learn how beta blockers act on beating heart

WEDNESDAY, May 1, 2002 (HealthDayNews) -- Opening a new frontier in cardiology, researchers have outlined the genetic mechanisms by which a class of drugs acts on the beating human heart -- a step that could lead to better medications targeted for specific cardiac conditions.

The drugs are beta blockers, used to treat high blood pressure and heart failure. Until now, says Dr. Michael R. Bristow, "the molecular details of how these agents help the heart and reverse some of the underlying pathology have not really been known."

Now, some of those blanks have been filled in because of a pioneering use of genetic technology.

In a study appearing in tomorrow's issue of the New England Journal of Medicine, 53 patients with dilated cardiomyopathy, a form of heart failure, were given either a beta blocker or a placebo. Then Bristow and his colleagues determined the activity of specific genes by measuring levels of RNA, a molecule produced by genes, in tiny tissue samples taken from the heart.

"We had candidate genes that might be involved in the reversal of heart failure," says Bristow, a professor of medicine and cardiology at the University of Colorado Health Sciences Center. "We measured five of them in the study, and three ended up in fact being involved. They are all part of a molecular program that controls contraction of the heart."

Similar studies have been done on human hearts that have been removed for transplantation, Bristow says, "but this is the first time that molecular changes have been measured in vivo [in the living heart]." In addition, he says, "the types of measurement that were used were unique to our technology."

The genetic discovery could have "a big clinical application," Bristow says. "It is further evidence that this gene program is a big player in the failing human heart and can be reversed by therapy. We think we can develop better therapies by generating compounds that do it better."

His group already is working with a biotechnology company to develop new medications for heart failure, Bristow says: "We're pretty excited about it."

"This begins to take us into a much more educated approach in using a therapy that we know works," says Dr. Lynne Warner Stevenson, co-director of the cardiology program at Brigham and Women's Hospital and author of a commentary that accompanies the report. "This type of research leads us to the next level of progress."

While cardiologists have known that beta blockers are effective in heart failure, "at the moment, we have a big gap between what we know and what we understand," Stevenson says. By learning how the drugs produce their beneficial effects, "we hope that we ultimately will be able to adjust treatments more effectively."

Sophisticated genetic testing might not be necessary, she says: "If we can find the molecular changes that occur, we can begin to look for other things that go with those changes that would be easier to measure. Then we can begin looking for blood tests or noninvasive tests so that we can monitor therapy as we go along."

One advantage of the technique is that it does not require a large number of subjects, Bristow says: "We did it in just 53 patients."

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"This study does not change clinical practice now," Stevenson says. "The information can help us select patients who will benefit most, the best doses we can use and, in some cases, the types of beta blockers that are best for patients."

To learn more about cardiomyopathy, go to the American Heart Association or the National Heart, Lung and Blood Institute.

SOURCES: Michael R. Bristow, M.D., professor, medicine and cardiology, University of Colorado Health Sciences Center, Denver; Lynne Warner Stevenson, M.D., co-director, cardiology program, Brigham and Women's Hospital, Boston; May 2, 2002, New England Journal of Medicine
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