Therapy with microRNA stimulates cardiac regeneration after a heart attack. Upper left, pig heart showing planes for cardiac magnetic resonance imagining (MRI). Upper right: MRI images at plane 3 of two pig hearts, one treated and one control, at 1, 4 and 8 weeks after infarction. The infarcted area is in red. Lower left: swine cardiac myocytes (green) with blue nuclei, connected through electrical junctions (red). Lower right: proliferating pig cardiomyocytes (green) in response to the microRNA (proliferating nuclei in pink)

Genetic therapy heals damage caused by heart attack

Researchers from the International Centre for Genetic Engineering and Biotechnology and King’s College London, UK have found that therapy that can induce heart cells to regenerate after a heart attack.

Myocardial infarction, more commonly known as a heart attack, caused by the sudden blocking of one of the cardiac coronary arteries, is the main cause of heart failure, a condition that now affects over 23 million population in the world, according to the World Health Organisation.

At present, when a patient survives a heart attack, they are left with permanent structural damage to their heart through the formation of a scar, which can lead to heart failure in the future. In contrast to fish and salamander, which can regenerate the heart throughout life.

In this study, published today in Nature, the team of investigators delivered a small piece of genetic material, called microRNA-199, to the heart of pigs, after a myocardial infarction which resulted in the almost complete recovery of cardiac function at one month later.

“It is a very exciting moment for the field. 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.” commented Professor Mauro Giacca who led the team of investigators.

This is the first demonstration that cardiac regeneration can be achieved by administering an effective genetic drug that stimulates cardiac regeneration in a large animal, with heart anatomy and physiology like that of humans.

“It will take some time before we can proceed to clinical trials” explained Giacca. “These experiments were performed using a virus to piggy-back the small RNA molecule into the infarcted heart cells, but this does not allow proper control of dose and time of administration, causing unwanted effects in the long term. 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”.

The study was a collaboration with the “Scuola Superiore Sant’Anna” and the “Fondazione Monasterio” hospital in Pisa, Italy, where investigators led by Professor Fabio Recchia performed the pig experiments.  Professor Giacca and his team joined the School of Cardiovascular Medicine & Sciences BHF Centre of Excellence of King’s College London from Trieste earlier this year to continue translation of these studies in patients.

Funding acknowledgements

This work was supported by a European Research Council (ERC) Advanced Grant and a Leducq Foundation Transatlantic Network of Excellence grant

con Mauro Giacca
Contact: Mauro.Giacca@icgeb.org