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Bare metal stents deliver gene therapy to heart vessels with less inflammation in animal studies

Improved materials may allow stents, tiny metal scaffolds inserted into blood vessels, to better deliver beneficial genes to patients with heart disease, by reducing the risk of inflammation that often negates initial benefits. The new technique, using a compound that binds in an extremely thin layer to bare metal surfaces, may have potential uses in other areas of medicine that make use of metallic implants.

Cardiologists frequently treat heart disease patients now by using stents to expand partially blocked blood vessels and improve blood flow. However, new obstructions may gradually form within the stents themselves and dangerously narrow the passageway. A newer generation of stents releases drugs to counteract this renarrowing process, called restenosis, but the polymer coatings that initially hold the drugs to the stents may stimulate inflammation. The inflammation in turn leads to restenosis.

Researchers at The Children's Hospital of Philadelphia have developed a novel technique to attach therapeutic genes to a stent's bare metal surface. This technique allows the genes to help heal the surrounding blood vessels, while avoiding the inflammation caused by polymer coatings.

The research team reported their proof-of-principle study, using cell culture and animal models, in the early edition of the Proceedings of the National Academy of Sciences, published online this week.

"This is the first study to demonstrate successful delivery of a gene vector from a bare metal surface," said senior author Robert J. Levy, M.D., the William J. Rashkind Chair of Pediatric Cardiology at The Children's Hospital of Philadelphia. A gene vector is a biological substance, in this case an adenovirus, capable of delivering a therapeutic gene to target cells.

Dr. Levy's team created a unique water-soluble compound, polyallylamine biphosphonate, that binds to the stent's metal alloy surface in a layer with the thickness of only a single molecule.
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Source:Children's Hospital of Philadelphia


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