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Abnormal heart rhythms afflict about one in every hundred Americans. For some people, these disturbances are basically harmless. For others, however, being out-of-sync disrupts the heart¿s coordinated pumping and leads rapidly to death. Current treatment options include drug therapy, pacemakers and defibrillators--which cannot cure the condition and have considerable downsides. But if the results of a study published in the December issue of the journal Nature Medicine are any indication, gene therapy may at last offer a long term solution. According to the report, researchers have developed for the first time a gene therapy that settles arrhythmias in pig hearts--the animal hearts that most closely resemble those of humans.
J. Kevin Donahue and his colleagues set out to develop a way to deliver a gene known as an inhibitory G protein gene to one of the heart¿s own pacemakers, a tiny region of tissue called the atrioventricular node (AV). When instructed by the nervous system, this gene acts to slow the heart rate. The team selected a standard gene delivery vehicle, the adenovirus, and then treated 10 pig hearts with agents that enhance uptake of this gene and its viral carrier. They subsequently injected the gene therapy. A week later, tissue studies revealed that the gene had reached nearly half of the AV node. What¿s more, says Donahue, "The AV nodes in the test hearts carried impulses at a significantly slower rate and were far less excitable than those in hearts without the added genes."
The team really put the genetically enhanced hearts to the test when they applied electrical and chemical stimulation that normally produces arrhythmia. Still the animals that had received the G protein gene exhibited a 20 percent decrease in heart rate as compared to control animals. This result is similar to that offered by so-called beta blockers, a common medication, the team notes. "But we believe the gene therapy that ultimately would help humans would, unlike beta blockers, be a long-term solution," Donahue offers. "Also, because gene therapy is localized to a specific place in the heart, it would avoid the side effects that come when beta-blockers travel to other parts of the body."
