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GENE THERAPY FOR BROKEN
HEARTS
By Sean Henahan, Access Excellence
BALTIMORE A genetic engineering experiment conducted
by cardiologists at Johns Hopkins University suggests that an effective
gene therapy for heart failure and irregular heartbeats is feasible.
A research team used an engineered gene to alter the beat of rat heart
muscle cells in the laboratory. They began with a fruit fly gene that creates
ion channels, special openings in the outer walls of cells that admit electrically
charged particles that, among other effects, stimulate cell contraction.
They then altered the fruit fly's gene so it produced ion channels that
stayed open longer.
The next step involved splicing the new gene into an adenovirus (a common
cold virus) and exposing rat heart cells to the virus in a Petri dish. Carried
into cells by the virus, the new gene produced altered ion channels that
allowed more charged particles to enter the cells. The scientists next injected
the new ion channel viral gene directly into newborn rats. The new gene's
products did appear in the rat's liver and heart cells.
This in vivo experiment was not designed to see if the new gene could
affect a living heart's behavior. To do this, Marban speculates, scientists
will first have to design a virus that specifically targets heart cells.
Repeated injections may then be needed to infect enough heart cells to change
the heart's behavior. Variations on this approach could help Marban and
coworkers not only change heart rates but also stabilize the electrical
properties of hearts susceptible to fatal irregularities of cardiac rhythm.
"We've shown that gene therapy doesn't only have a future for very
rare genetic disorders, but also may one day be a treatment for very common
disorders such as arrhythmias and heart disease," says Eduardo Marban,
M.D., Ph.D., professor of medicine and physiology, at Johns Hopkins.
"What we've done shows that it's possible to alter the action potential
of cells both in the lab and in a living animal through the use of recombinant
adenovirus technology," Marban says. "With appropriate targeting,
such a strategy may be useful in gene therapy not only of arrhythmias, but
also of seizure disorders and muscle diseases--any disorder marked by an
electrical impulse.
"We've taken the first step on a very long road. We've shown that
it's essentially possible to do these things; now the question shifts to
more strategic issues like how do we deliver the gene efficiently to the
target tissue and how do you keep the body from rejecting the new gene,"
he says.
The experiments were published in the July 28, 1995 issue of the Journal
of Clinical Investigation.
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