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Researchers develop gene therapy to reverse pulmonary arterial hypertension

A University of Alberta research team has discovered important new information they hope will lead to more effective treatments for pulmonary arterial hypertension (PAH)--a deadly form of high blood pressure in the pulmonary arteries caused by uncontrolled cell growth. Therapies are currently limited for a disease that can lead to heart failure and death within a few years.

The researchers have shown that Survivin, a protein almost exclusively expressed in cancer, is also heavily expressed in both human and animal lung arteries with PAH. Survivin is an inhibitor of apoptosis--or programmed cell death--which promotes cancer by suppressing the body's ability to limit excessive cell growth.

Armed with this new information and using animal models, the researchers developed a nebulized and inhaled gene therapy to deliver an inactive Survivin-mutant via a virus--known in science as a "dominant negative construct"--effectively inhibiting endogenous Survivin. The therapy reversed PAH in rats and improved their heart function and their survival, thus holding out some promising avenues of treatment for human PAH. The team members believe that as in cancer, Survivin drives excessive cell growth in the PAH lung blood vessels.

"The most intriguing aspect," explains principal researcher Evangelos Michelakis, "is we've shown for the first time that this cancer protein is also expressed within the blood vessels of the lung in patients suffering with PAH, but not in normal human blood vessels, making survivin a very attractive target for selective intervention.

"This makes the proliferation of lung blood vessels in this disease a 'form of cancer' or a form of neoplasia to be more precise, first proposed by Drs. Voelkel and Tuder from the University of Colorado. We've demonstrated for the first time that, like cancer, apoptosis is suppressed in the lung blood vessel wall in this disease."

"Our biggest challenge in treating PAH is the fact we don
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Source:University of Alberta


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