A new approach that combines a traditional surgical treatment with gene therapy could make operations on clogged coronary arteries more successful. Robert Levy and his colleagues sought to improve the angioplasty procedure, in which an expandable, metal scaffold (or stent) is used to extend and unblock clogged heart arteries. A common problem is that although the procedure are effective in treating the initial obstruction, the benefits typically last only a few months because cells soon repopulate and block the artery-a condition called restenosis. Levy and his team believe that stents with a polymer containing a gene that inhibit growth of cells in the arterial wall may offer a better prognosis for patients undergoing angioplasty operations. In the present study (Nature Biotechnology, 01 Nov 2000), they show that such an approach is feasible in principle.
In test-tube experiments simulating the arterial environment, Levy and his collaborators showed that a stent coated with a gene-impregnated polymer released the gene over a ten-day period. The gene stayed intact and was capable of entering cultured cells: after a piece of stent metal coated with the DNA-impregnanted polymer was placed on cultured rat artery muscle cells, about 8% of cells that were in contact or near to the metal rod expressed the gene. And in experiments involving pigs, about 1% of cells from the walls of coronary arteries that had received stents coated with the polymer-DNA mixture expressed the gene five to seven days later. Moreover, gene expression was largely restricted to the coronary arteries, spreading only minimally to other organs.
The results are encouraging and support the use of stents for targeted, sustained delivery of therapeutic genes to the arterial wall, particularly as the long-term use of catheters to deliver DNA solutions can be impractical and imprecise. Further work is required to identify the gene(s) most effective in preventing restenosis.
Dr. Robert J. Levy
Children's Hospital of Philadelphia
Abramson Research Center, Suite 702
3516 Civic Center Blvd
Philadelphia, PA 19104-4318
Tel: +1 215.590.6119
Fax: +1 215.590.5454
(C) Nature Biotechnology press release.
Message posted by: Trevor M. D'Souza
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