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Gene therapy repairs heart attack damage

27 August 2013
Appeared in BioNews 719

Researchers have concocted a 'gene cocktail' that may help to turn scar tissue into functioning cardiac cells after a heart attack.

Scar tissue often forms following a heart attack in the area that was most affected. The result is a decreased ability of the heart to beat properly and can eventually lead to heart failure. The scientists, from the Gladstone Institutes in San Francisco, USA, are working with cells called fibroblasts, which make up about half of all heart cells. They are aiming to reprogram the function of these fibroblasts from primarily providing structural support to beating heart cells by injecting a cocktail of genes.

In 2012 the team found that by directly injecting three cardiac genes, collectively referred to as GMT, they observed decreased scar size and improved cardiac function in mice. In this study, they tested this procedure on human cells, but found that using the same GMT combination in human fibroblasts was not enough.

'When we injected GMT into each of the three types of human fibroblasts, nothing happened - they never transformed - so we went back to the drawing board to look for additional genes that would help initiate the transformation. We narrowed our search to just 16 potential genes, which we then screened alongside GMT, in the hopes that we could find the right combination', explained lead author Dr Ji-dong Fu.

The authors were able to identify four additional genes that, together with GMT, promoted reprogramming in human fibroblast cells. With the addition of these genes, around 20 percent of all treated cells could then function like beating heart cells, including being able to transmit electrical signals.

Within the UK, around 750,000 people have heart muscle that is severely damaged by a heart attack and are at risk for heart failure. It is estimated that within five years this damage will kill three-quarters of patients affected. Finding a way to improve treatment of this damaged tissue could eventually improve patient outcome long term.

The findings of this study are a proof of the concept that human fibroblasts have the ability to be reprogrammed into beating heart cells. However more research will be needed to make the process more efficient.

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation told The Telegraph that 'this research represents a small but significant step forward'.

Direct Reprogramming of Human Fibroblasts toward a Cardiomyocyte-like State
Stem Cell Reports |  22 August 2013
Gladstone Scientists Transform Non-Beating Human Cells into Heart-Muscle Cells
Gladstone Institutes (press release) |  22 August 2013
Heart attack damage repaired using gene therapy
Daily Telegraph |  22 August 2013
Scientists use gene therapy to repair muscles damaged in heart attacks
The Independent |  22 August 2013
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