Innovative method for gene therapy of heart disease shows promise in animal studies

November 07, 2000

Philadelphia, Pa. -- Heart disease patients may someday receive a dose of gene therapy that would protect injured coronary arteries from further damage and possibly even treat the underlying heart disease. The genes would be delivered to artery walls by stents, the tiny metal scaffolds that are now implanted in diseased arteries to hold the vessels open for improved blood flow.

In cell cultures and in pigs, a team led by a researcher from The Children's Hospital of Philadelphia showed that genes in DNA added to the stents were transferred into cells on the artery wall. The study appeared in the November issue of the journal Nature Biotechnology.

"This is the first example of gene transfer in an animal model using stents for DNA delivery," said Robert J. Levy, M.D., director of the Pediatric Cardiology Research Laboratory at The Children's Hospital of Philadelphia. "The technique has major implications for treating coronary artery disease with gene therapy."

Stents are commonly used in angioplasty procedures for partially blocked coronary arteries. After a small balloon is inserted through a catheter and inflated to widen a narrowed artery (the angioplasty procedure), an expandable wire scaffolding (the stent) is left in the artery to keep it open. However, in approximately 30 percent of patients, stents injure the artery, causing cells to grow back within a few months, often forming new obstructions.

The gene delivery technique employed by Dr. Levy's team would release a gene or combination of genes that can help control blood vessel damage by inhibiting cell growth in the artery walls. "Further research is needed to identify genes that would have the most beneficial effect," said Dr. Levy, "but this study in animals shows that the gene delivery technique is possible."

Delivery is a crucial problem in any gene therapy approach. Unlike other approaches that uses viruses as delivery vehicles to carry genes into the body, Dr. Levy's group uses DNA within a biodegradable film that coats the metal stents. The technique allows a controlled release of the DNA into cells in the arterial wall, with only minimal spread of the DNA beyond the arteries.

The stent-based technique, says Dr. Levy, may be used in the future for localized gene therapy: the targeted delivery of DNA to a specific site with fewer of the side effects that may occur with systemic gene therapy. Further determination of the most appropriate genes for treating artery disease must occur before the gene-coated stents can be studied in humans.

Co-authors with Dr. Levy are from The Children's Hospital of Philadelphia and the University of Pennsylvania Medical Center. The study was partially supported by a grant from Selective Genetics, Inc., a biotechnology company in San Diego, Cal. Stents were supplied by the Cordis Corporation of Warren, N.J.
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Founded in 1855 as the nation's first pediatric hospital, The Children's Hospital of Philadelphia is recognized today as one of the leading treatment and research facilities in the world. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique outreach and public service programs have brought the 381-bed hospital recognition as a leading advocate for children from before birth through age 19.

Children's Hospital of Philadelphia

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