New mRNA therapy wakes up heart muscle cells to repair damage

Scientists have developed a treatment that “wakes up” heart muscle cells so they start dividing and help repair damaged muscles.

In a study in mice, this produced a louder heartbeat and increased the amount of blood pumped through the heart with each heartbeat by about 10%, compared to mice that received sham treatment after a heart attack.

Although not a complete cure, even small improvements in heart function have been associated with lower mortality in patients and an improved ability to carry out daily activities.

The treatment uses mRNA therapy to temporarily activate two proteins inside heart cells, called Myc and Cyclin T1, thereby promoting repair of heart tissue.

This could potentially be used in the future to treat patients with heart failure. In the UK, around 200,000 people are diagnosed with heart failure each year and, although current treatments can reduce symptoms and slow the progression of heart disease, they cannot regenerate already lost heart muscle.

These are truly exciting results. There is no cure for heart failure, and our treatment could potentially have a significant impact on the quality of life of millions of people around the world. »

Dr Catherine Wilson, Associate Professor, Department of Pharmacology and Gurdon Institute at the University of Cambridge, co-senior author of the study

She added: “We’re not just treating the symptoms of heart failure: this approach could help the heart repair itself.”

The team is currently working to refine the treatment and has received funding from the British Heart Foundation to continue their work. Further testing in larger animal models and then in humans is needed to fully establish its safety and effectiveness.

The results are published today in the journal Nature Cardiovascular Research.

Test the treatment

After a heart attack, the mRNA therapy was injected into the hearts of mice and its effectiveness was assessed by examining the hearts with an echocardiogram – like looking at a baby in the womb.

Because the treatment is short-term and localized, it is not expected to cause permanent changes to heart cells – designed to reduce the risk of proliferation, and no adverse effects were observed in the mice.

Re-evaluation of the mice after 28 days and after 12 weeks showed that the improvement in cardiac function was lasting.

Can we teach the heart to heal itself?

After a heart attack, an adult human heart can lose up to a billion heart muscle cells. Unlike many other organs in the body, the adult heart cannot regenerate, so lost cells are never replaced. Their loss reduces the strength of the heart and can lead to scarring, heart failure and ultimately death.

As the world’s population grows and the prevalence of heart failure increases, the cost of patient care is expected to increase significantly. Scientists believe that waking up heart muscle cells in this way is a promising approach to treating heart failure patients.

Professor Bryan Williams, scientific and medical director of the British Heart Foundation, said: “Getting the human heart to repair itself is the holy grail for cardiologists. The heart repairs itself easily when we are babies in the womb, but our heart muscle cells lose the ability to regenerate and repair the heart shortly after we are born.

“It makes it exciting that studies like this are able to jump-start the regeneration of heart muscle cells. The gene therapy used by the researchers shows clear potential for heart patients. Although the research is in mice, and still at an early stage, it represents an important step forward toward therapies that could help repair damage to the heart following a heart attack.”