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'Smart gene therapy' protects against damage from heart attack

cle are available, most patients barely make it to the hospital in time to take advantage of them," Dzau said. "This smart gene therapy could be administered preemptively to high- risk patients months before they develop a heart attack to provide them with long-term protection from ischemic injury. The minute this gene is switched on following a loss of blood flow, levels of the therapeutic protein rise rapidly, providing near-complete protection."

In patients with myocardial ischemia, the loss of blood flow causes the heart tissue to slowly or suddenly starve of oxygen and other nutrients. Eventually, said Dzau "little bits of heart muscle get chewed away" as tissue dies, weakening the organ and resulting in failure. When blood flow becomes blocked completely, a heart attack can ensue. Physicians may be able to reopen narrow or blocked heart vessels with balloon angioplasty, but restoration of blood flow often leads to inflammation and tissue injury. Ischemia also can occur in arteries of the kidneys, lungs, liver or the brain, where it leads to stroke, he added.

The team developed a "therapeutic gene construct" that contains both DNA sequences that can detect oxygen deficiency and a therapeutic human gene -- heme-oxygenase 1 -- that has been shown to protect cells. They then inserted the gene construct into a harmless virus known as adeno-associated virus, whose job was to transport the therapeutic gene into the genetic material of the rat's cells.

"We're trying to create a physiological on-off switch that will automatically turn on the therapeutic gene when ischemia causes dangerous levels of oxygen deprivation," Dzau said. "Such internal regulation is ideal for safe and effective gene therapy."

The researchers injected the gene construct into the heart, liver and skeletal muscle of three rats in the laboratory. Five weeks later, they restricted blood flow to the animals' organs by clamping key arteries for a period of an hour and
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-660-1306
Duke University Medical Center
2-Aug-2004


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