MEDICINE
NOVEMBER 22, 1999 VOL. 154 NO. 21
How To Mend A Broken Heart
In one of the first success stories to come out of gene-therapy research, doctors are learning how to teach the heart to heal itself
BY CHRISTINE GORMAN
Every year some 400,000 Americans undergo bypass surgery to shunt the flow of blood around blocked arteries in their heart; 500,000 other patients opt for a different procedure called angioplasty, which clears a channel through the bottlenecks with thin, inflatable balloons. Most people who have these operations get what they so desperately want--a second chance at life. But the results are usually temporary. After a few years the bypass graft or the reopened artery becomes clogged with new deposits, which often require a second round of treatment. For an estimated 1 in 10 patients, the heart becomes so scarred that nothing more can be done.
That grim outlook may be about to change. Scientists have
been experimenting with a new way--based on a form of gene
therapy--to coax the heart into
growing new blood vessels to replace old worn-out ones,
and doctors who have been performing the procedure are becoming
more and more excited by the results. Reports of their progress
have spread through the scientific community for the past
year. But not until last week, when the leading researchers
gathered in Atlanta at a brainstorming meeting to which TIME
was given exclusive access, did it become clear how far they
have gone. Says Dr. Todd Rosengart of the Northwestern University
Medical School: "Because we're looking at a different way
of providing blood flow, we're making a step toward what could
be a long-term cure for heart disease."
Already, 1,000 patients have received
the experimental therapy at 50 different medical centers.
In most cases the treatment was part of a conventional bypass
or angioplasty. But the preliminary results were so encouraging
that doctors have started offering the new therapy to patients
who are too sick to undergo any more conventional operations.
There are still many unanswered questions, and some patients
have died (although researchers insist their deaths did not
occur as a consequence of the treatment). Yet if the new therapy
lives up to its promise, hundreds of thousands of men and
women with heart disease will, over the next few years, be
able to heal themselves.
Doctors have long known that the heart can, in response
to a drop in the level of oxygen-rich blood it's receiving,
grow extra blood vessels. But the process, called angiogenesis,
is often too slow and not extensive enough to stave off a
heart attack. About 10 years ago, scientists started identifying
certain proteins, called growth factors, that the body uses
to build new blood vessels. The proteins act like foremen
at a construction site, making sure that all the pieces of
the project come together smoothly. Animal experiments showed
that there were several ways to get growth factors into the
heart. You could inject a gene--either by itself or wrapped
in a viral envelope--that tells the heart muscle how to make
growth factor. Or you could skip the gene and just use the
finished product, the growth-factor protein itself. The advantage
of gene therapy is that you have to do it only once; the gene
will keep generating growth-factor protein. Using the protein
by itself gives doctors a little more control. The disadvantage
is that they may have to repeat the process, perhaps as frequently
as every few months.
Whether genes or proteins are used, the goal is the same, to blanket the heart with lots of little blood vessels. (Surprisingly, you can reach more of the heart muscle with a lot of little blood vessels than with a few big ones.) But that presents another problem. The blood vessels are so small that they are impossible to see even with today's highest-resolution heart scans.
As a result, there is still no objective evidence that angiogenesis therapy improves blood flow to the heart. Yet all other signs indicate that something good is happening. Patients experience much less chest pain, or angina, and can run much longer on a treadmill. Although encouraging, such quality-of-life reports are not enough to convince other doctors, not to mention the Food and Drug Administration, that the treatment is effective. Researchers are confident, however, that improvements in imaging technology will soon allow them to detect the presence of the new blood vessels that they believe are there.
Until then, angiogenesis therapy seems to be giving another chance to a growing number of patients who thought they had run out of options. And as anyone with heart disease can tell you, sometimes that's all you need.
--REPORTED BY ALICE PARK/ATLANTA
