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Heart Therapy Aims to Harness Body's Power


About 14 million Americans suffer from coronary artery disease, which can transform routine daily activities into gasp-for-breath tasks. But many of them are poor candidates for the most commonly performed repairs.

For those patients, doctors have been studying chemicals that encourage the creation of tiny, new channels to get around clogged arteries, essentially inducing patients to grow their own bypasses.

Promoting the creation of those new blood vessels--through a process called angiogenesis--to fight heart disease is a nifty concept that patients would welcome as an alternative to bypass and angioplasty. But it can be thorny in practice, as researchers are learning.

Angiogenesis studies have become the hot new frontier in medicine.

At medical schools and biotechnology companies, angiogenesis researchers are racing to unlock the mysteries of what makes blood vessels flourish--or wither away. Finding those answers, they hope, could lead to potentially lucrative treatments for heart disease, cancer, blindness, arthritis and psoriasis.

The search began nearly 30 years ago, when Dr. Judah Folkman, a researcher at Boston Children's Hospital, suggested angiogenesis was an essential process in cancer. By cutting off a tumor's blood supply, and thus its supply of nutrients and oxygen, he proposed doctors could literally starve a tumor to death--a notion ridiculed by many colleagues. Soon afterward, he helped discover a molecule that would stop blood vessel formation--a first step toward demonstrating the merit of his theory. Since that time, scientists have identified more than 300 other angiogenesis inhibitors.

Although the field has blossomed in the last few years, many people may have first heard about angiogenesis in May 1998, when a controversial front-page article in the New York Times quoted Nobel Prize winner Dr. James Watson as saying that Folkman's anti-angiogenesis work in mice could lead to a cancer cure in two years. Scientists said the mouse research was far too preliminary for any claims about cures.

As Folkman and colleagues around the world try to stop angiogenesis in tumors, many cardiac researchers want to encourage it within the heart. They're trying to harness the power of new blood vessels to move nourishing blood through weakened hearts. In 1997, researchers announced with great fanfare that they were able to grow new arteries in the legs of heart patients with poor circulation using a gene for vascular endothelial growth factor.

Looking at the Results of a Promising Study

Last week, thousands of heart doctors jammed a room at the American College of Cardiology meeting in Anaheim to learn about the results of a much-anticipated angiogenesis study. It was designed to determine whether a genetically engineered protein called basic fibroblast growth factor could stimulate the growth of new vessels in diseased hearts. The therapy had looked promising in earlier studies involving animals, and researchers were hopeful it would work in humans.

But the results, many meeting participants said, were kind of a bust.

The study, sponsored by a Northern California-based biotechnology company, Chiron Corp., involved 337 patients with severe coronary artery disease, some of whom received a single infusion of the protein directly into the heart, and others who received a placebo, a dummy treatment. To evaluate the effectiveness of the protein treatment, the researchers looked for improvement in the patients' endurance during physical exercise.

After three months, the group that got the protein reported being able to exercise on a treadmill for an additional 65 seconds; those on the placebo improved their endurance by 45 seconds--a statistically insignificant difference.

Researchers were encouraged, however, by two other findings. The oldest and sickest patients reported less chest pain, or angina. Using nuclear imaging, doctors saw that their hearts indeed had sprouted new blood vessels.

One of the study's lead investigators, Dr. Michael Simons, head of angiogenesis research at Beth Israel Deaconess Medical Center in Boston, said these secondary findings gave researchers an idea of which patients might benefit the most from angiogenesis and were promising enough to warrant further study.

At the same meeting, Dr. Jeffrey Isner, a cardiologist with St. Elizabeth's Medical Center in Boston, reported positive results of a small preliminary study of 30 heart disease patients treated with another vascular growth factor. Twenty-one patients reported significantly fewer episodes of chest pain; nine of them were pain-free.

Premature Assumptions Could Give False Hope

Such results, some doctors warn, tend to raise the hopes of heart patients who may be too sick to endure open-heart surgery or who are poor candidates for the artery-clearing procedure known as angioplasty. That is why it is important, for the medical community--and the media--to be careful about not hyping the results of early studies.

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