The phase II clinical research study uses vascular endothelial growth factor-2 (VEGF-2) in the form of a solution containing a DNA plasmid that is delivered using catheterization to heart tissue that has been damaged from insufficient blood flow.
Once the catheter reaches the targeted site inside of the heart, the VEGF-2 is injected into the heart muscle region with inadequate blood supply. The DNA plasmid is then taken up by the middle muscular layer of the heart wall near the injection site. Inside the cell, the DNA encoded VEGF-2 expresses itself which in turn stimulates the growth of new blood vessels by promoting the proliferation of endothelial cells in the heart.
New blood vessels are required to provide oxygen-carrying blood to heart muscles to compensate for the blocked heart arteries. The subsequent, improved blood flow relieves the painful symptoms of angina.
"The process of growing new blood vessels, or angiogenesis, should occur over the course of four to eight weeks following the procedure which is done in the cardiac catheterization lab at Rush," said Dr. Gary L. Schaer, the principal investigator of the trial at Rush and director of the Rush Cardiac Catheterization Labs. "The patient goes home the next day." Several patients have received the gene therapy and all are doing well.
Individuals who may be candidates for this gene therapy study trial must have moderate to severe angina, but cannot also be candidates for treatment using angioplasty or bypass surgery. Angioplasty involves a catheterization with a balloon-like device that opens blocked arteries, while bypass surgery requires open-heart surgery to place veins removed from the patient's leg or arteries taken from the patient's chest wall or arm to "bypass" the blocked blood vessels.
While both of these treatments have been shown to be successful in relieving severe chest pains resulting from blocked arteries, a significant percentage of patients eventually do not respond well to either treatment, often requiring another angioplasty or bypass operation, noted Schaer. "If gene therapy proves to be safe and effective, it will represent an important new approach to improve the quality of life in these seriously ill patients with refractory chest pain," said Dr. R. Jeffrey Snell, study co-investigator and Schaer's colleague at Rush.
In the new study, patients will be randomly assigned to receive the gene administered through a cardiac catheter threaded into the heart from a leg artery or a placebo delivered using the same method. As required by the U.S. Food and Drug Administration, the study is "double blinded," which means that neither the doctor nor the patient will know whether he or she is receiving the gene therapy or a placebo. For every three patients that receive the active gene, one will receive a placebo. Following treatment, patients enrolled in the study will be examined for chest pain at one month, three months and six months. A total of 404 patients will be enrolled in the study at the 20 study sites across the country.
The Genetic Angiogenic Stimulation Investigational Study (GENASIS) is funded by Corautus Genetics.
More than 11 million people in the United States suffer from coronary artery disease. Many patients receive medications to increase blood flow but nearly 500,000 angioplasties and coronary bypass procedures are performed each year in those patients who do not benefit from medication.