Gene Therapy

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Cardiovascular Disease Causes and Treatment

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Cardiothoracic Surgeon

Associate Professor of Surgery Cornell University New York, New York

Therapeutic angiogen-

esis is a promising new treatment for artery blockages typically caused by atherosclerosis. Angiogenesis means the "formation of new blood vessels." In angiogenesis, a naturally occurring protein called a growth factor, or angiogen, is used to stimulate blood vessel growth. This enhances blood flow to tissues that are jeopardized by a blockage.

In the laboratory, therapeutic angiogenesis has been shown to help blood vessels develop. Among other actions, angiogen-esis might reduce the effects of atherosclerosis, enhance wound healing, and promote tissue growth. It may be particularly useful for patients with such severe or widespread atherosclerotic disease that they cannot be fully helped by conventional therapies like angioplasty or bypass surgery.

Besides using growth protein, we are also considering gene therapy. To do this, we transfer genes directly into a targeted tissue, where the gene "turns on"

DNA that causes cells to produce the proteins that cause growth of new blood vessels. Genes can be transferred on genetically engineered viral particles. The adenovirus (Ad) is one such viral particle that efficiently transfers genes to tissues such as the myocardium, or heart muscle. Genes transferred by Ad remain in the tissue they are sent to and are active for only one or two weeks. This is important because it potentially prevents the overproduction of a protein that might cause abnormal blood vessel growth.

We have so far tested the Ad protein transfer technique in twenty-one patients. These patients had not responded to coronary bypass surgery or coronary balloon dilatation because of the severity of their coronary artery disease. To date, the gene therapy appears to be well tolerated, and we plan to move into larger-scale human studies. Similar positive results have been reported by other investigators using a "naked" DNA segment that was not incorporated into a viral particle like Ad.

It is unknown which, if any, gene therapy strategy will work best, or whether they will be superior to the use of angiogenic proteins themselves instead of the genes for these proteins. Finally, it is unknown which, if any, of the many angiogenic proteins will work best, or which delivery method will be most beneficial. Preliminary studies and the promise of future advancements are, however, very encouraging.

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