For the first time, scientists have demonstrated that a genetic therapy can regenerate heart tissue after heart attack injury in a large mammal.
'It is a very exciting moment for the field,' said lead researcher Professor Mauro Giacca at King's College London. 'After so many unsuccessful attempts at regenerating the heart using stem cells, which all have failed so far, for the first time we see real cardiac repair in a large animal.'
Cardiac muscle cells do not regenerate in mammals after birth. So after a heart attack, the cardiac muscle remains permanently damaged, which often leads to heart failure and death.
The team showed that injecting a piece of human genetic material called microRNA-199 into pigs after a heart attack stimulated cardiac repair. One month after the heart attack and treatment, all the treated animals showed improvement in their cardiac function, as well as increased cardiac muscle mass and reduced scar tissue.
MicroRNA-199 had previously been shown to stimulate cardiac muscle cells to enter the cell cycle, leading to more cell division and an increase in heart muscle cell production.
While this process initially resulted in production of more heart cells that healed the existing damage, it could not be stopped once the heart regenerated. This led to overproduction of cardiomyocytes. As a consequence, most of the treated pigs died of sudden arrhythmic death.
'It will take some time before we can proceed to clinical trials,' said Professor Giacca. 'We still need to learn how to administer the RNA as a synthetic molecule in large animals and then in patients, but we already know this works well in mice.'
'A treatment that helps the heart repair itself after a heart attack is the holy grail for cardiologists,' said Professor Ajay Shah, British Heart Foundation chair of cardiology at King's College London. 'Professor Giacca's study convincingly demonstrates for the first time that this might actually be feasible and not just a pipe-dream. It's a very exciting advance in the field.'
Heart attacks affect approximately 920,000 people in the UK alone. The new study was published in Nature.