Readers may remember positive patient profiles from earlier coronary gene therapy trials at St. Elizabeth's Medical Center of Boston (which have as yet not resumed).

Now a trial is investigating the potential of a new and different gene protein to promote the growth of blood vessels to the heart. Called fibroblast growth factor IV (FGF4), the protein is entering Phase II/III testing at the Indiana Center for Vascular Biology and Medicine (ICVBM)/Krannert Institute of Cardiology.

Preliminary data demonstrate safety of the innovative gene therapy concept, as reported last April. "There is no product approved to stimulate the growth of new blood vessels," noted Cindy Grines, M.D., lead author of the study that appeared in Circulation and director of the cardiac catheterization laboratories at William Beaumont Hospital in Royal Oak, Michigan. "We think the growth factor gene used here restarts this natural response. This is a completely new and different approach."

In July, ICVBM will begin enrolling patients in the Angiogenic GENe Therapy (AGENT 3) trial under the direction of Dr. Jeffrey Breall, director of cardiac catheterization and interventional cardiology for Krannert Institute of Cardiology, and Dr. Keith March, director of ICVBM.

"The purpose of the trial is to facilitate formation of bypass vessels by accelerating a natural process called angiogenesis or collateral vessel formation," Dr. March explains. "Some people are able to grow vessels sufficiently on their own, but many do not. The idea of this trial is to use this adenoviral vector that has the great capability of transducing or sending genes into cells very well and efficiently. By carrying this gene vector into the coronary circulation, it should help the cells that form coronary blood vessels grow. For people with few or no conventional treatment options for angina, we hope this therapy will help grow bypass vessels and reduce chest pain."

Unlike studies at St. Elizabeth's, participants in the AGENT 3 trial could be candidates for other therapies.

"This trial serves a broader population," says Dr. Jeffrey Breall. "These people could potentially have an angioplasty, bypass, or other interventions, but if it seemed these may not be optimal therapy for the best long-term results, their physicians may deem them eligible for this trial."

Gene therapy has demonstrated great potential in stimulating the body's natural ability to grow new blood vessels--a process called angiogenesis--in oxygen-deprived areas of heart muscle damaged by coronary heart disease.

"FGF4 is a protein that causes the growth of blood vessels by stimulating both the endothelial and smooth muscle cells," Dr. March told Neighborhood Heart Watch. "It has been shown in preclinical and in Phase I and II patient studies that FGF4 helps the vessels to grow faster, decreases angina, and reduces ischemia."

Patients with stable class II-IV exertional angina due to coronary artery disease are eligible to participate in this multicenter, randomized, double-blind, placebo-controlled clinical trial.

If you would like to learn more about participating in the AGENT 3 trial at ICVBM, contact Julie Lacy, R.N., B.S.N., Clinical Research Coordinator, Indiana Center for Vascular Biology and Medicine, 975 West Walnut St., IB441, Indianapolis, IN 46202 or call 317-962-0138.