- DALLAS (AP) -- For the first time, doctors have shown that by inserting
genes into the heart, they can enable patients to grow their own bypasses.
The approach could someday spare patients the need for surgery, in which
a piece of blood vessel is grafted into place to create a detour around
- 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.
- 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 only does its work 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 blood-starved muscle and relieve crippling
- 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 and others reported their findings
Monday at a meeting of the American Heart Association in Dallas.
- 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
last 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.
- Among his patients is Floyd Stokes, a
58-year-old peanut farmer from DeLeon, Texas. For the past two years, he
had been so handicapped by chest pain that he could walk no more than 100
yards and did most of his work from the seat of his pickup truck.
- Stokes underwent the procedure on May
26. Within three weeks, he began to feel better. Now, he said, he walks
and works as much as he wants, completely without pain.
- "One Sunday morning I woke up and
told my wife I hadn't felt so good in 15 years," he said. "I
- Stokes and other patients underwent an
hour-long surgical procedure, in which doctors cut a small hole in the
chest wall and injected the genes into their hearts.
- Isner said his team hopes to make the
process easier by using a catheter threaded through an artery into the
heart to deliver the genes. Animal studies have shown this should work.
- 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.
- Crystal's team has treated 21 patients
-- 15 during bypass surgery, six as the sole therapy. "Clearly the
trend is toward improvement," he said, even though it's too soon to
judge how well his approach worked.
- Instead of injecting bare strands of
DNA, as Isner used, Crystal created a hybrid cold virus to carry the VEG-F
gene into heart cells.
- Tests suggest that once installed, the
gene produces blood vessel-promoting proteins for two or three weeks and
then stops working. However, this apparently is long enough to grow a permanent
new blood supply.
- How long the improvement lasts remains
to be seen, and Dr. Valentin Fuster, president of the heart associate,
- "We think it will work," he
said, "but how much? What will be the impact?"