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Byline: Daily News Staff and Wire Services

For the first time, doctors have shown that by inserting extra genes into the heart, they can stimulate the growth of new blood vessels, enabling patients to grow their own bypasses.

The discovery, announced Monday at a meeting of the American Heart Association in Dallas, will be tested by UCLA cardiologists as part of a nationwide clinical trial.

``It would be bypass surgery without bypass surgery,'' said Dr. Michele Hamilton, associate clinical professor of cardiology at the University of California, Los Angeles, and co-director of the heart failure program. ``If it works, it can be extremely beneficial to a large number of patients.''

The discovery could someday spare patients the need for bypass surgery, in which a piece of blood vessel is grafted into place to create a detour around a blockage. Hamilton said the experimental gene therapy could provide hope for patients too sick or weak to undergo conventional treatments.

Experts say this new gene-insertion procedure, tested initially in the legs and now in the heart, represents the first example of gene therapy actually correcting a human ill.

UCLA will participate in clinical trials by early next year, Hamilton said. Patients whose blood vessels are significantly blocked and whose hearts are not receiving enough blood, will be eligible for the trials.

Several competing teams of doctors have injected a gene that makes a protein called vascular endothelial growth factor - or VEG-F, pronounced vedge-eff - into the hearts of people who have clogged vessels but are too sick to undergo ordinary bypass surgery or angioplasty. Ordinarily, the gene does its work only during fetal development in the womb.

The doctors found clear, and in some cases dramatic, evidence that the gene prompts the heart to sprout tiny new blood vessels to nourish the blood-starved muscle and relieve crippling chest pain.

Nevertheless, the procedure is still highly experimental and is probably several years away from routine use.

``We are trying to take damaged adult organs and return them to youth,'' said Dr. Ronald G. Crystal of Cornell Medical School in New York City. He was among several doctors who reported their findings Monday.

At UCLA, the patients will receive the genes through a catheter to blood vessels in the heart.

``This is the first time that we've had something that may help the heart grow more blood vessels,'' Hamilton said. Until now, physicians have used bypass surgery or angioplasty to dilate clogged blood vessels feeding the heart.

``If this technique proves successful, it will allow improvement of blood supply to the heart in a large pool of patients,'' Hamilton said.

While the gene therapy appears to be promising, it would not be helpful in emergency heart attack surgery, Hamilton said, because the new heart vessels need time to grow.

``It would be useful for people who chronically are not getting enough blood supply to their hearts,'' she said.

Still unclear is whether this kind of genetic manipulation will work any better than a more direct medical approach - giving people doses of the protein made by the gene. At a conference in March, doctors from the University of Minnesota showed that the VEG-F protein appeared to ease angina in 13 of 15 patients treated.

Among those receiving injections of the VEG-F gene were 16 patients of Dr. Jeffrey Isner of St. Elizabeth's Medical Center in Boston, all of them heart attack victims who suffered excruciating chest pain at even the mildest exertion.

Some of Isner's patients were taking as many as 60 nitroglycerin tablets a week for their pain. Now all have improved substantially, and the average dose is 2-1/2 pills weekly. Of the 11 patients who have been followed up for at least three months, six are entirely free of pain.

A variety of tests, including nuclear scans, show improved blood flow to the patients' heart muscle, even though the blood vessels created by the treatment are too small to be seen.

``We are extremely encouraged about this therapy,'' Isner said.

At the outset, Isner said, gene therapy might help the 250,000 U.S. patients annually who have severe chest pain that cannot be corrected with bypass surgery or angioplasty. At some point, however, it might be an alternative even for those in early stages of disease who have had no other treatment.
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Publication:Daily News (Los Angeles, CA)
Date:Nov 10, 1998

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