Gene Therapy Shows Promise for Treating Heart Attack Victims

Injections of a normally silent gene sparked recovery in pigs induced to have heart attacks

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When a heart attack brings blood flow to a screeching halt, thats only the first assault on our fist-size organ. Among survivors, the recovery itself fuels more permanent damage to the heart. Scar tissue can harden once-flexible heart muscle, making it less elastic. And as tentacles of this tissue creep over the aorta the heart muscle can no longer fully contract. This long-term damage can minimize the amount of oxygen-rich blood sent throughout the body, which can send patients spiraling into heart failure. Heart transplants are one way to circumvent these scar tissue issues, but donor hearts are always in short supply. Devising other truly effective solutions has long eluded researchers. A form of gene therapy, however, is now showing promise in pigs. It turns out that a normally silent gene called Cyclin A2, or CCNA2, can be coaxed into action to combat the formation of scar tissue in pigs that suffer a heart attack. This treatment sparked regeneration of heart muscle cells in pigs as well as improvements in the volume of blood pushed out with every beat. The finding is published in the February 19 issue of Science Translational Medicine. Gene therapy, the authors hope, may one day join stem cell treatments as a contender for transforming the way doctors treat heart failure. Stem cellbased therapies have already resulted in more healthy tissue and decreased scar mass in human clinical trials as well as small improvements in how much blood the heart can pump from one chamber to another. But as Scientific American reported in April 2013, many questions remain about which stem cells to use and how to prepare them. For this study, researchers randomly assigned 18 pigs recovering from heart attacks to either receive injections of the gene expressed under a promoter (which would force it to be expressed) or the same solution without the gene. Pigs treated with the gene had greater success pushing out blood with each heartbeat, but also produced a greater number of heart muscle cells. These findings echo the teams earlier heart regeneration successes in mice and rats. The researchers replicated their findings in a petri dish and watched adult porcine heart muscle cells treated with the same regimen of gene therapy undergo complete cell division in the dishdemonstrating under a microscope how the heart cells were dividing and thriving with the gene therapy. This new approach mimics the kind of regeneration we see in the newt and zebra fish, says lead author Hina Chaudhry, the director of cardiovascular regenerative medicine at The Mount Sinai Hospital in New York City. If the technique proves successful in humans, it could boost patient recovery rates by helping strengthen heart muscles and improving blood flow, all while giving a needed lift to gene therapy research, which has been slow to gain momentum in the U.S. In 1999 Jesse Gelsinger, 18, died after a gene therapy experiment cost him his life. The virus used to deliver a gene that would potentially control his rare digestive disorder fueled a massive and fatal immune reaction. That highly publicized case, along with other gene therapy missteps, put a pall on the field. Chaudhry says that her team is proceeding with caution and plans to be careful when administering this treatment to patient populations. For patients who have a large heart attack who are at risk of heart failure, I think the therapy is going to be very beneficial, she says. If you have a small heart attack, it probably wont make as much of a difference in overall survival because of advances with todays medicines. As more researchers look to gene therapy for previously intractable human conditions, a success with heart attack treatments could send ripples throughout the field.

2014 Scientific American, a Division of Nature America, Inc.

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Gene Therapy Shows Promise for Treating Heart Attack Victims