tPA Gene Therapy Clears Clots. to blocked leg arteries - Stanford researchers' novel method for delivering tissue plasminogen activator tPA - Technology Information

Applied Genetics News, April, 1999

Stanford researchers (Contact: Ruthan Richter; Tel: 650/723-6912, Email: richter1@stanford.edu) have devised a novel method for delivering tissue plasminogen activator (tPA) to blocked leg arteries, restoring blood flow to the damaged vessels. The method was outlined by Michael Kuo, a radiology resident at Stanford University, at the March 22 meeting of the Society of Cardiovascular and Interventional Radiology.

The researchers inserted the tPA gene into a healthy leg vein in rabbits, using an disabled adenovirus vector. The veins began turning out large quantities of tPA. They then used the vein as a bypass for an adjacent artery that was constricted by a clot. The procedure reduced clotting by 75% and effectively restored blood flow in the treated rabbits. The technique could potentially benefit millions of patients with peripheral vascular disease (PVD) in which plaque builds up in the leg arteries, sometimes causing debilitating pain and difficulty in walking. As many as 5% of men and 2.5% of women over the age of sixty have symptoms of PVD. Current treatment involves injecting tPA or other clot-busting drugs into the patient's bloodstream. A drawback of this treatment is that it can induce bleeding throughout the body. "We're taking a vein and making it into a superstructure that is resistant to clots," says Kuo. "Because it (tPA) is locally delivered, bleeding is virtually non-existent." The new technique could theoretically be adapted to coronary bypass procedures, which often fail due to arterial clotting. The tPA gene could be inserted into the saphenous vein, the vein most commonly used for bypasses, before removing it. Doctors could then sew the now clot- resistant vein into the chest to bypass the clogged cardiac arteries.