Clot-Busting Gene Triggers Blood Vessels to Become Self-Cleaning

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CLOT-BUSTING GENE TRIGGERS BLOOD VESSELS

TO BECOME SELF-CLEANING

ORLANDO, Fla. -- Researchers have moved a step closer to creating "self-cleaning" blood vessels by using a new technique to transplant a gene that breaks down blood clots in arteries, according to a study presented here today at the 24th Annual Scientific Meeting of the Society of Cardiovascular & Interventional Radiology (SCVIR).

"Although this approach is still under investigation, we feel it has great potential," said Michael Kuo, M.D., Radiology Resident, Stanford University Medical Center, and researcher at Stanford Institute for Bioengineering and Molecular Medicine, Stanford, Calif. "It may be beneficial in combating blood clots in the heart and leg vessels, atherosclerosis (plaque build-up) and, eventually, may even be used in cancer therapy, as well as many other diseases."

Researchers used the human tissue plasminogen activator (tPA) gene to break down blood clots created in the leg arteries of rabbits. A drug derived from the tPA gene currently is used as an emergency heart attack and stroke treatment. The technique has potential to combat the problem of peripheral vascular disease (PVD), in which plaque builds up in leg arteries -- just as it does in heart vessels -- and which causes leg pain and a subsequent decrease in activity. As many as 5 percent of men and 2* percent of women age 60 and older have symptoms of PVD.

The technique involves a several-step process:

Researchers create an adenovirus that has lost the ability to replicate. It is an extremely safe virus that normally is a cause of the common cold.

They insert the tissue plasminogen activator (tPA) gene in the virus, which is in a saline solution. The gene has been cloned from the human body.

The solution is injected into a vein and left to sit for 15 minutes. The solution is then removed from the vein.

The vein is removed surgically and attached, or grafted, to an artery which is nearly 100 percent blocked by a blood clot.

Researchers found that 6 days after treatment, the clot occupied only 7 percent to 20 percent of the artery in all 5 subjects. Comparatively, 6 days after treatment, the clot occupied greater than 75 percent of the artery in control groups of 5 subjects each -- one group of which received a placebo, and the other which received a different gene than the tPA gene.

Previous attempts to inject the virus with the gene directly into affected leg arteries have failed because the clot or plaque formed a physical barrier to the gene. Treating a normal vein turns it into a super factory of tPA, creating high levels of the gene that can break through the clot or plaque.

This approach also appears to alter the physiology of the vein so that it takes on the characteristics of an artery, which is larger and can more easily handle the circulatory pressures. This overcomes two current problems with blood vessel grafting:

Although arteries are preferable for grafting, only two are commonly used.

While there are more veins available for grafting, they often fail because they tend to develop blood clots or plaque after being grafted.

Co-authors of a paper on the topic being presented by Dr. Kuo are: Jacob M. Waugh, M.D.; Esser Yuksel, M.D. and Michael D. Dake, M.D.

An estimated 5,000 people are attending the Annual Scientific Meeting in Orlando, Fla., of SCVIR, a professional society based in Fairfax, Va., for physicians who specialize in minimally invasive interventional procedures.

An interventional radiologist is a physician who has special training to diagnose and treat illness using miniature tools and imaging guidance. Typically, the interventional radiologist performs procedures through a very small nick in the skin, about the size of a pencil tip. Interventional radiology treatments are generally easier for the patient than surgery because they involve no surgical incision, less pain and shorter hospital stays.

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Copies of 1999 SCVIR news releases are available online at www.pcipr.com/scvir beginning Monday