An experimental treatment developed by scientists at the University of Cambridge has shown promise in helping regenerate muscle damaged during a heart attack, according to a study published in the journal Nature Cardiovascular Research.
The approach encourages repair of injured heart muscle after a cardiac arrest by “reawakening” heart muscle cells so they start to divide and help repair damaged tissue. Because adult heart cells cannot repair themselves once damaged, the research team says the breakthrough marks an important step towards a potential curative treatment for heart disease.
Promising results in mice
In a study in mice, the treatment produced a stronger heartbeat and increased the amount of blood pumped through the heart with each heartbeat by around 10%, compared with mice that received a mock treatment, following a heart attack. While it is not a complete cure, the Cambridge team says that even modest improvements in heart function have been linked to lower patient mortality and a greater ability to carry out day-to-day activities.
The treatment uses mRNA therapy to temporarily activate two proteins inside heart cells, called Myc and Cyclin T1, promoting repair of heart tissue. The researchers say it has the potential to be used to treat patients with heart failure.
Potential impact on heart failure
Around 200,000 people in the UK are diagnosed with heart failure each year, and while existing treatments can ease symptoms and slow the progression of the disease, they cannot regenerate heart muscle that has already been lost. Around 1.4 million people alive in the UK today have survived a heart attack, says the British Heart Foundation.
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. We’re not just treating the symptoms of heart failure - this approach could help the heart to repair itself.”
Long-lasting improvement and next steps
Following a heart attack, the mRNA therapy was injected into the hearts of the mice and its effectiveness assessed by looking at the hearts with 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. Reassessing the mice after 28 days and after 12 weeks showed that the improvement in heart function is long-lasting.
After a heart attack, an adult human heart can lose as many as one billion heart muscle cells, and unlike many other organs in the body, an adult heart cannot regenerate itself, so these lost cells are never replaced. This loss reduces the strength of the heart, which can lead to scar formation, heart failure and ultimately death.
As the global population grows and heart failure becomes more common, the cost of caring for patients is expected to rise sharply. The Cambridge team believes that reawakening heart muscle cells could be a promising way to treat people with heart failure.
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.
Professor Bryan Williams, chief scientific and medical officer at the BHF, 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.”
