Scientists have regenerated cardiac muscle in pigs with heart failure.
Heart failure occurs when the organ is unable to pump blood around the body efficiently, usually because it has become too weak or stiff.
Writing in the journal Science Translational Medicine, scientists from the Texas Heart Institute in Houston describe how the muscle cells within an adult's heart have "poor renewal capacity".
Heart failure therefore generally worsens over time, severely limiting a patient's activities and often becoming fatal.
To better understand the potential of gene therapy, the scientists "knocked down" the so-called Hippo signalling pathway in the cardiac muscle cells of pigs after the animals endured a heart attack – a cause of heart failure.
This caused the pigs' cardiac cells to divide, "resulting in effective tissue renewal with improved heart function" and "an opportunity for repair after injury in humans".
Nearly a million people have heart failure in the UK. Heart-related complications are behind more than a quarter of all deaths.
Heart failure treatments aim to control its symptoms – namely breathlessness, fatigue and swollen legs – and slow the condition's progression.
Whether lifestyle changes, medication or surgery, treatment is usually life-long.
The Hippo signalling pathway is thought to suppress the division and renewal of adult cardiac muscle cells after a heart attack.
To better understand the potential of gene therapy, the Houston scientists analysed pigs after they endured an induced heart attack.
Two weeks later, the animals had "dysfunction" in their left ventricle, affecting their hearts' ability to pump blood.
In some of the pigs, a catheter injection delivered a harmless virus carrying genetic material that "turned off" the animals' Hippo pathway gene Salvador.
The remaining pigs acted as the control group and were injected with a virus carrying a fluorescent protein.
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Three months later, the pigs' hearts that were treated with a "high dose" of the genetic material-carrying virus experienced a 14.3% improvement to their ejection fraction – a percentage of blood that is pumped out of the heart during each beat, acting as a measurement of the organ's function.
This is "evidence" the pigs' heart muscle cells divided, as well as demonstrating reduced "scar sizes" compared to the control animals, according to the scientists.
The treated pigs also had increased capillary density. Capillaries are the smallest blood vessels, which distribute oxygen-rich blood from arteries to bodily tissues.
Overall, the gene therapy was "well tolerated and did not induce mortality".
Although it is early days, the scientists believe the gene therapy "may have utility in treating heart failure" in humans.
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