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Gene therapy for hibernating hearts
  
By Bijal P. Trivedi

Researchers are using a gene to stimulate the growth of blood vessels in the hearts of patients with severe ischemic heart disease.

For patients with this disease, large regions of heart muscle are unable to pump blood effectively because the vessels feeding the area clogged, depriving the cells of oxygen and causing sharp chest pain.

As part of an early Phase-1clinical trial a team of scientists led by Jeffrey Isner, of Tufts University School of Medicine in Boston, injected DNA containing the gene, vascular endothelial growth factor (VEGF), directly into the damaged areas of the heart through a one-inch opening between the ribs.

After 60 days the 13 patients in the study were examined using two imaging systems to determine whether blood flow to the oxygen-impoverished regions had improved. One system is non-invasive and uses radioactive isotopes to visualize changes in circulation. The other technique, electromechanical mapping (EMM), involves inserting the instrument at the groin and threading it up to the left ventricle of the heart where it measures the electrical activity of over 100 sites in the heart. The electrical measurements are used to create 3D maps of the heart indicating which areas are healthy and pumping blood and which are ischemic or completely dead.

The researchers said that circulation to many regions of the ischemic, or hibernating, heart muscle had been restored. The patients also reported on average fewer than five episodes of chest pain per week compared to more than 48 before the therapy. The results were published in a recent issue of Circulation.

"The results presented in this paper are an incremental advance, another small step for cardiovascular gene therapy but not a home run," says Cam Patterson, of the University of North Carolina, Chapel Hill, co-author of an editorial in the same issue of the journal. This is not a randomized trial, and it lacks the proper controls, says Patterson.

The technique used by Isner's team, with three invasive procedures, is not practical for severely ill patients. If the initial EMM procedure could be combined with the administration of the gene, then this may eventually evolve into a viable therapy, says Patterson.

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Patterson, C. & Runge, M.S. Therapeutic myocardial angiogenesis via vascular endothelial growth factor gene therapy: Moving on down the road. Circulation 102, 940-942 (August 29, 2000).
 
Vale, P.R. et al. Left ventricular electromechanical mapping to assess efficacy of phVEGF165 gene transfer for therapeutic angiogenesis in chronic myocardial ischemia. Circulation 102, 965-974 (August 29, 2000).
 

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