A new study published in Science claims that a novel experimental therapy that uses RNA technology to help the heart heal itself after a heart attack could be a less invasive technique to stop long-term heart failure. Researchers at Columbia University say the approach allows the body to produce a protective heart hormone through a simple injection in the arm, potentially opening a new path for treating cardiac damage.

After a heart attack, doctors can reopen blocked arteries using procedures such as stents to restore blood flow, but the heart muscle cells that die during the event are rarely replaced. This leaves many patients with permanent damage that can later develop into heart failure.

“The heart is one of the organs with the least ability to regenerate,” said Ke Cheng, Alan L. Kaganov Professor of Biomedical Engineering at Columbia Engineering. “The spontaneous regeneration power is very, very limited.”

The new treatment aims to boost the heart’s natural repair system by increasing levels of a hormone called atrial natriuretic peptide, or ANP. This hormone helps reduce inflammation, encourage new blood vessel growth and limit scar formation after cardiac injury.

“You don't have to open the chest or send a wire to the heart to deliver this drug,” Cheng said. “In principle, all the clinician needs to do is inject the particles into the arm.”

The idea emerged from observations that newborn mammals briefly possess the ability to regenerate heart muscle. During the first days of life, their bodies produce large amounts of ANP after cardiac injury, allowing damaged tissue to recover more effectively. As individuals age, however, production of the hormone drops sharply and the heart’s regenerative ability fades.

In experiments comparing newborn and adult mice after heart attacks, researchers found that the gene responsible for producing the precursor to ANP increased more than 25 times in newborn hearts but only about ten times in adult hearts. When scientists blocked that gene in newborn animals, their hearts lost much of their ability to heal.

“The whole idea is that we learn from nature,” Cheng said. “The neonatal heart spontaneously produces more of this molecule after a heart attack. That's probably why young hearts can regenerate themselves. The adult can't produce a sufficient amount, so we found a way to supplement this supply to the heart.”

Delivering medicines directly to the heart has long been a challenge because most drugs do not naturally accumulate in cardiac tissue. The current approaches often require invasive procedures performed in specialised cardiac catheterisation laboratories.

“Because of these challenges, researchers have worked on cardiac drug delivery with infusions directly into the blood vessels of the heart, injections into the heart muscle, and injections into the pericardium, which is the sac surrounding the heart,” said Torsten Vahl, a physician at Columbia University Irving Medical Center. “All of these methods are invasive and need to be performed in a cath lab.”

Instead of targeting the heart directly, the research team designed RNA-lipid nanoparticles that instruct muscle cells in the arm or thigh to produce a harmless precursor molecule called pro-ANP. This compound circulates in the bloodstream until it reaches the heart, where an enzyme known as 'corin' converts it into active ANP.

“Targeting is based on a specific cleavage of an enzyme that is naturally expressed in the heart,” Cheng said. “The idea is that you don't have to touch the heart or open the chest. All you need to do is to inject the arm.”

The scientists used a special form of self-amplifying RNA that allows cells to keep producing the molecule for several weeks after a single injection. In laboratory studies involving both small and large animals, the treatment significantly reduced scar formation and improved heart function.

“As a clinician who opens up arteries with stents for patients who come to us with heart attacks, I am highly aware that we have a large unmet need for our patients,” Vahl said. "Many times, patients suffer from severe heart damage, which later leads to heart failure."

The therapy also showed benefits for animals with conditions that often complicate heart disease, including diabetes, atherosclerosis, and ageing. Researchers believe the approach could eventually provide a more affordable alternative to complex treatments such as heart transplantation or stem-cell therapy.

Beyond heart attacks, scientists say the RNA delivery strategy could potentially be adapted to treat other diseases involving organ damage.

“Cell damage is a problem that not only affects the heart but also many organs,” Vahl said. “If we can prove that this type of therapy can regenerate cardiac cells in the clinical setting, the idea could potentially be transferred to other organs.”

The research team now plans to manufacture the therapy and launch early-stage human safety trials at Columbia’s medical center— a step that could determine whether the promising laboratory findings can translate into a new treatment for patients recovering from heart attacks.