January 5, 2013
Damaged Heart Strengthened Using New Gene Therapy Method
redOrbit Staff & Wire Reports - Your Universe Online
A team of US researchers has reportedly developed a way to reprogram scar tissue from damaged hearts into healthy muscle through gene therapy -- a discovery which could help strengthen hearts harmed as a result of cardiovascular events.According to a recent statement, scientists from Weill Cornell Medical College, along with colleagues from the Baylor College of Medicine (BCM) and Stony Brook University Medical Center have discovered a combination of three specific genes can turn cells in the scar tissue into fully-functioning muscle cells, and the addition of a fourth can stimulate blood vessel growth and make the process even more effective.
Typically, the heart's blood supply is cut off during a heart attack, causing muscles to die off and become scarred, the researchers explained. The result is a weakened heart which will eventually lead to heart failure for those who have experienced serious cardiovascular events. This, however, could be avoided if medical experts could find a way to transform scar tissue into normal heart tissue, thus strengthening the heart as a whole.
To that end, Dr. Todd K. Rosengart, chair at BCM's Michael E. DeBakey Department of Surgery, and colleagues implanted either three forms of a gene that encourages blood vessel growth -- known as the vascular endothelial growth factor (VEGF) gene -- or an inactive material into the hearts of rats.
"Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material. (A transcription factor binds to specific DNA sequences and starts the process that translates the genetic information into a protein)," the researchers explained. "The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT."
"The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. (Ejection fraction refers to the percentage of blood that is pumped out of a filled ventricle or pumping chamber of the heart)," they added. "The hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer."
"The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting," Dr. Rosengart, the corresponding author of the study, said. "The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that even the effect is enhanced when combined with the VEGF gene."
"This experiment is a proof of principle. Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts," added Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College. "We have shown both that GMT can effect change that enhances the activity of the heart and that the VEGF gene is effective in improving heart function even more."
Their findings have been published online in the Journal of the American Heart Association.