Bare Metal Stents Deliver Gene Therapy to Heart Vessels
News Dec 21, 2005
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 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.
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 technique to attach therapeutic genes to a stent's bare metal surface.
This technique is designed to allow 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.
Dr. Levy's team created a 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.
The biphosphonate holds and gradually releases adenovirus particles of the type used to deliver therapeutic genes.
In cell cultures, the adenovirus delivered genes from alloy samples to animal arterial smooth muscle cells.
In a second experiment using rodents, the researchers detected gene expression with significantly lower restenosis in the carotid arteries of animals with the experimental stents, compared to control animals with conventional, polymer-coated stents.
The researchers used a therapeutic gene that encodes for a protein, inducible nitric oxide synthase (iNOS), in the carotid artery studies, because of iNOS's ability to control cell damage in blood vessels.
"However, in further studies, one might use a combination of therapeutic genes or different gene vectors, for even better results," said Dr. Levy.
"The results of our study may have broader implications for other diseases in which implantable medical devices may be used to deliver gene therapy," said Dr. Levy.