Researchers at the University of Cambridge have developed an experimental mRNA treatment that could help repair heart muscle after a heart attack, with early results described as encouraging. The study, published in Nature Cardiovascular Research, found that the treatment "reawakens" heart muscle cells, prompting them to divide and repair damaged tissue.
In tests on mice, the treatment led to a stronger heartbeat and boosted the amount of blood pumped with each beat by about 10% after a heart attack, compared with mice given a mock treatment. While it is not a complete cure, the Cambridge team says that even modest gains in heart function have been associated with lower mortality and an improved ability to manage everyday activities.
How the treatment works
The therapy uses mRNA to briefly switch on two proteins in heart cells – Myc and Cyclin T1 – helping to stimulate repair of damaged heart tissue. After a heart attack, the mRNA therapy was injected directly into the mice's hearts, and its effectiveness was assessed using an echocardiogram.
Since the treatment is short-lived and localised, it is not expected to cause any permanent modification to the heart cells – designed to reduce the risk of overgrowth – and no adverse effects were seen in the mice. When the mice were reassessed after 28 days and again at 12 weeks, the improvement in heart function was shown to be long-lasting.
Potential for heart failure patients
The researchers say the approach could potentially be used to treat people with heart failure. Around 200,000 people in the UK are diagnosed each year and, while current treatments can relieve symptoms and slow the disease's progression, they cannot replace heart muscle that has already been lost.
After a heart attack, an adult human heart can lose up to a billion heart muscle cells and, unlike many other organs, it can't regenerate, meaning those cells are never replaced. Losing these cells weakens the heart, which can cause scarring, lead to heart failure and, in the end, prove fatal.
Experts react to the findings
Study co-senior author Professor Catherine Wilson said: "These are really exciting results. There's no cure for heart failure, and our treatment could potentially have a meaningful impact on the quality of life of millions of people around the world." She added: "We're not just treating the symptoms of heart failure - this approach could help the heart to repair itself."
Professor Bryan Williams, chief scientific and medical officer at the British Heart Foundation, said: "Getting the human heart to repair itself is the holy grail for cardiologists. The heart is easily repaired when we are babies in the womb, but our heart muscle cells lose the ability to regenerate and fix the heart shortly after we are born. That makes it exciting when studies like this are able to reignite regeneration in heart muscle cells."
He added: "The gene therapy used by the researchers shows clear potential for heart patients. While the research is in mice, and still at an early stage, it is an important step forward towards therapies which could help repair the damage to the heart following a heart attack."
The team is now working to refine the treatment and has received funding from the British Heart Foundation to continue the work. Further trials in larger animal models, followed by studies in humans, are needed to fully confirm its safety and effectiveness.
