RNA against heart attacks

Researchers are hoping to be able to use non-coding therapeutic RNA ‒ snippets of genetic information ‒ to allow cardiac muscle to regenerate following a heart attack. By Caroline Ronzaud

​(From "Horizons" no. 106, September)
Image: © Keystone / Science Photo Library

One of the manifestations of a heart attack is the death of sections of cardiac muscle. Over a certain limit, this sometimes leads to heart failure. According to Thierry Pedrazzini, professor in experimental cardiology at the Vaud University Hospital Centre (CHUV) in Lausanne, the heart of adult mammals is unfortunately incapable of auto-regeneration. Whilst it does contain progenitor cells, which are similar to stem cells and necessary for regeneration, the quantities are not large enough. Furthermore, these cells are not naturally inclined to produce new cardiac muscle cells.

To get the heart to create new cells and hence restore cardiac function, regenerative medicine has for a long time placed its chips on cellular therapy providing the solution through the use of injected stem cells. But results in human and mouse experiments have let them down, showing improvements in heart functioning but not any production of cardiac muscle – except in a recent study in primates with embryonic stem cells. We also need to show that this method does not lead to tumours, says Mauro Giacca, Director of the International Centre for Genetic Engineering and Biotechnology in Trieste, Italy. “It’s also slow and difficult to set up”, he says.

Reprogramming heart cells

A new approach, however, involves reprogramming cardiac muscle cells to activate the molecular mechanisms in the heart that are responsible for creating muscle. The CHUV has set out to study this, using non-coding RNA: short segments of genetic information that do not produce proteins. “RNA are like switches for the genes, allowing proteins to be produced at the right time and in the right place, for example during stress or to differentiate stem cells”, says Pedrazzini. “There are different types of RNA in every type of cell, making them excellent therapeutic targets”.

The researchers have identified the non-coding RNA molecules that control the differentiation of stem cells in cardiac muscle. They have since been able to stimulate the regeneration of an adult mouse heart following a cardiac arrest. They were also able to produce a culture of muscle cells using progenitor cells taken from the hearts of patients suffering from heart failure. “For a long time we believed that adult muscle heart cells could not divide,” explains Pedrazzini. “However, this ability can be reactivated through the manipulation of non-coding RNA, without having to use stem cells”.

Thomas Thum, director of the Institute of Molecular and Translational Therapeutic Strategies in Hanover, Germany, also sees the interest in non-coding RNA therapy. “What still needs to be resolved, however, is increasing the efficacy and finding a way to administer active substances into patients’ hearts”.