Innovative gene therapy approach to prevent amputations in patients suffering severe peripheral artery disease

Cardiologists at Rush University Medical Center are studying an investigational medication to prevent amputations in patients suffering the most severe form of peripheral arterial disease. The study involves use of a highly innovative gene therapy approach to promote new blood vessel growth in the legs of patients with critical limb ischemia.

Researchers at Rush are enrolling patients in a Phase III clinical trial called the TAMARIS study to evaluate the product’s effectiveness in preventing amputations in patients suffering from critical limb ischemia, which is a severe lack of blood flow in a lower limb.

“At this time there are no prescription drugs available to effectively treat critical limb ischemia, and there are limited treatments available that will delay or prevent amputation,” said Dr. Jeffrey Snell, study principal investigator and interventional cardiologist at Rush.

Peripheral artery disease (PAD) is a vascular disease in which the arteries that carry blood to the legs become narrowed or clogged due to formation of plaque, interfering with normal blood flow. These plaques can rupture causing clots to form, which can further block the arteries.

Because of this poor circulation, the tissues then become starved of the nutrients and oxygen they need and skin ulcers begin to form. The later stages of PAD are the most serious and are referred to as critical limb ischemia. This is when the possibility of amputation is present.

“The goal of gene therapy is to stimulate the growth of new blood vessels. The additional blood vessels will carry more blood into the legs, alleviating pain and healing ulcers,” said Snell.

The trial involves an angiogenesis therapy developed by Sanofi-aventis that is based on Vical’s non-viral DNA delivery technology. The plasmid DNA therapy induces the production of a protein called fibroblast growth factor (FGF-1) which stimulates the growth of blood vessels at the site of injection.

During the 12 months study, participants will receive four injections of the investigational study medication or a placebo into the leg muscle at two-week intervals. Qualified participants will receive all study-related care at no cost including physical exams, study medication, eye exams, and cancer screenings.

To participate in the study, individuals must be 50 years of age or older, have stable skin ulcers or non-infected gangrene on a foot or leg, be diagnosed with Peripheral Artery Disease (PAD) at the stage of critical limb ischemia and be unsuitable for standard revascularisation.

According to the American Heart Association, PAD affects approximately 8 million people or about 1 in 40 adults in the United States. PAD is a common and chronic disease that is often under diagnosed. If the arteries in the legs are affected by atherosclerosis, other arteries are likely to be affected as well.

(Source: Rush University Medical Center: January 2009)