A single injection of a therapeutic drug like mRNA could help the heart muscle heal after a heart attack in mice and pigs. Is it also effective for humans?

A single shot of self-amplifying RNA can repair tissue damage caused by a heart attack, a new study in pigs and mice shows.

It can take weeks or even months to recover from a heart attack, but a new study has explored a new way to boost the production of natural heart repair hormones with a single injection. Although the vaccine has not yet been tested in humans, researchers believe it may one day offer hope for a faster recovery.

“This system is revolutionary because it uses skeletal muscle as a factory to produce the proteins we need,” study co-author Dr. Ke Huang, assistant professor of pharmacy at Texas A&M University, told Live Science.

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Heart attacks are often caused by clogged arteries that prevent oxygen-rich blood from reaching the heart muscle. Surgery can remove the blockage, but the heart muscle itself must also recover from oxygen deprivation. If it doesn’t heal quickly enough, scar tissue takes its place, making it less effective at pumping blood and can lead to heart failure.

“Heart disease remains the No. 1 killer in the United States,” said Ke Cheng, a biomedical engineer at Columbia University and lead author of the new study. Repairing heart muscle cells after a heart attack could reduce the risk of death from heart failure, but doing so comes with challenges. “It’s very difficult to deliver drugs to the heart without invasive procedures,” Chen told Live Science.

In a study published March 5 in the journal Science, Chen and his colleagues showed that a single injection of self-amplifying RNA (saRNA) into the muscle tissue of the hind limbs can increase levels of a hormone called atrial natriuretic peptide (ANP) and heal heart muscle cells in mice and pigs.

Researchers learned from mouse studies that ANP levels in newborns are much higher than in adults. The researchers attributed this difference to ANP’s role in heart development. Inspired by this, Cheng and colleagues investigated whether it was possible to temporarily increase ANP levels in adult mice to aid heart healing. “We wanted to see if we could supplement ANP with self-amplifying RNA,” Cheng said.

Once injected, saRNA tells muscle tissue to produce a molecule called proANP. proANP enters the bloodstream and is converted to ANP when it reaches the heart.

This mechanism is similar to how mRNA vaccines work. Like mRNA, saRNA contains instructions for making proteins. Both mRNA and saRNA degrade within a few days, but saRNA tells the cell to make more copies of itself, allowing the cell to continue regenerating and producing proteins for about four weeks.

The first saRNA-based COVID-19 vaccine has been approved for use in Japan and Europe, but saRNA has never been used in cardiac therapy before.

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“I think this is a perfect use for saRNA,” said Anna Brackney, a biomedical engineer at the University of British Columbia who studies saRNA but was not involved in the study. She pointed out that mRNA is useless for such studies because it disappears quickly. While this is enough for vaccines to activate the immune system, saRNA is more effective for applications that require larger amounts of protein.

Although this new method of increasing ANP has not been tested in humans, it can help restore heart cells in mice and pigs. Because saRNA is effectively a longer form of mRNA, it uses the same delivery system as the COVID-19 vaccine, which bodes well for the safety of the shot itself. Nevertheless, future research will need to determine how much ANP is safe and effective in humans.

“We still don’t know exactly what mechanisms could be advantageous for patients,” said Dr. Dan Attar, a professor of cardiology at Oslo University Hospital who was not involved in the study. He noted that previous studies treating heart attack patients with natriuretic peptides (such as ANP) had no effect on recovery, so this new single-delivery method needs to be proven in clinical trials.

More research is still needed on this potential treatment, including trials to confirm the mechanism, test the safety of the injection, and monitor its effectiveness. But once these steps are passed, it could be a promising means of healing the heart after a heart attack.