- The Washington Times - Tuesday, August 29, 2000

Physicians in Boston have injected a gene into the hearts of chronically ill heart-attack victims, provoking the growth of new blood vessels and dramatically improving heart health.
Although the clinical trial marks the third attempt at this type of gene therapy, it is "the first study using objective findings that has demonstrated improvement in blood flow to the heart," says Dr. Jeffrey M. Isner.
The trial is unusual because of the way the gene was delivered.
In previous trials, the genes were encapsulated in a virus. Dr. Isner's team defied conventional wisdom and directly and successfully injected small, circular pieces of DNA called plasmids into the heart. DNA is the molecule that contains the gene.
Commenting on the significance of the trial, Dr. Isner said: "There has been great concern about whether gene therapy works. This is very solid evidence that it does."
Dr. Isner is professor of medicine and pathology at Tufts University School of Medicine and a pioneer in the use of gene therapy to treat heart disease. He led the team that injected the gene into the hearts of eight men and five women who were experiencing severe heart pain.
The gene, called VEGF (for vascular endothelial growth factor), promotes blood-vessel development. It was inserted into the heart through a 1-inch diameter "keyhole" chest incision.
All the chronically ill patients in the trial had experienced at least one heart attack. All had undergone bypass surgery. And all but one had undergone balloon angioplasty one or more times to open clogged arteries. Yet all continued to suffer chest pain.
Six months after the gene injections, the average number of "angina episodes," or pain attacks, for the group had plummeted from 48 per week to 2. And the average weekly intake of pain-fighting nitroglycerin tablets dropped from 55 to 2.
Significantly, the exercise tolerance of the patients nearly doubled. The length of time the patients could tolerate stress testing rose from 4.5 minutes to 7.5 minutes.
Using heart scans and a system of computer mapping, the doctors found that, as hoped, the flow of blood to the heart had increased. In some patients, areas of the heart presumed to be dead were revived.
Heart attacks occur if the blood flow to the heart stops. When that happens, certain portions of the heart tissue die, or, in some instances, seem to die and are said to "hibernate."
Dr. Marschall S. Runge explained in an interview that the blood-starved portion of the injured heart is like "the sun-scorched grass of a summer lawn."
"You can't tell whether it's really dead until you water it. If it starts to turn green, it was only hibernating. If it stays brown, it was dead," he said.
In the gene trial cases, blood entering the hearts via newly grown blood vessels rejuvenated the tissue. So obviously the tissue was hibernating, not dead.
Dr. Runge, chairman of the department of medicine at the University of North Carolina Medical School in Chapel Hill, wrote a commentary to accompany Dr. Isner's report in today's issue of the journal Circulation, an American Heart Association publication. He called Dr. Isner's work "a breath of fresh air for cardiovascular specialists and their patients."
He concluded that the progress of gene therapy in stimulating blood flow to the damaged heart is "extraordinary given the slow progress of gene therapy in other fields."

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