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Gene therapy reprograms scar tissue in damaged hearts into healthy heart muscle

NEW YORK (Jan. 4, 2013) — A cocktail of three specific genes can reprogram cells in the scars caused by heart attacks into functioning muscle cells, and the addition of a gene that stimulates the growth of blood vessels enhances that effect, said researchers from Weill Cornell Medical College, Baylor College of Medicine and Stony Brook University Medical Center in a report that appears online in the Journal of the American Heart Association.

"The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting," said Dr. Todd K. Rosengart, chair of the Michael E. DeBakey Department of Surgery at BCM and the report's corresponding author. "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," said Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College and a pioneer in gene therapy, who played an important role in the research. "Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts."

During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart. Eventually, most people who have had serious heart attacks will develop heart failure.

Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery, Rosengart and his colleagues transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) 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.)

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Ancient sites spotted from space, say archaeologists

Jason Ur said he had found about 9,000 potential new sites in north-eastern Syria.

Computers scanned the images for soil discolouration and mounds caused when mud-brick settlements collapsed.

Dr Ur said surveying the same area on the ground would have taken him a lifetime.

Writing in the Proceedings of the National Academy of Sciences, the researcher told BBC News: "With these computer science techniques, however, we can immediately come up with an enormous map which is methodologically very interesting, but which also shows the staggering amount of human occupation over the last 7,000 or 8,000 years.

"What's more, anyone who comes back to this area for any future survey would already know where to go.

"There's no need to do this sort of initial reconnaissance to find sites. This allows you to do targeted work, so it maximises the time we have on the ground."

In the past, Dr Ur used declassified spy satellite photographs and the human eye to try to identify potential sites.

But over the last three years, he has worked with computer expert Bjoern Menze, from the Massachusetts Institute of Technology, to create a software application able to classify a huge range of terrain.

He said this had removed subjectivity and allowed them to look at a much larger area.

In all, about 9,000 possible settlements were identified across 23,000 sq km.

Ideally, he said, some of these would be excavated, but the volatile political situation in Syria had forced them to put any ground searches on hold.

However, he did tell the BBC that he hoped to conduct further research in the Kurdish provinces of northern Iraq, and follow that up with excavations that would be "a very rigorous testing of the model".

Archaeological work in Iraq has not been popular in the past, but Dr Ur feels the time is right to identify heritage sites of importance and ensure they are not lost as the country presses on with widespread development of its towns and cities.

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