Experimental RNA drug helps hearts heal after heart attacks

A heart attack does more than block blood flow. Inside your body, it unleashes chaos. Heart cells flood with harmful oxygen molecules. DNA strands snap. Protein-making systems fail. Immune alarms roar to life. In hours, heart tissue begins to die. Days later, inflammation hardens into scar tissue. Over time, the heart weakens and may fail.

Now, scientists say a tiny piece of synthetic RNA could change that story.

In a study published in Science Translational Medicine, researchers at Cedars-Sinai report that an experimental drug called TY1 helped damaged hearts heal in laboratory animals. It did not thin blood or open arteries. Instead, it worked deep inside immune cells to repair DNA and quiet inflammation.

Cedars-Sinai executive director Eduardo Marbán, MD, PhD, calls it something new. “TY1 is the first exomer, a new class of drugs that address tissue damage in unexpected ways,” he said.

The path to TY1 began more than 20 years ago at Johns Hopkins University. Scientists there learned how to isolate special heart support cells called progenitor cells. Later, after Marbán moved to Cedars-Sinai, his team made a discovery that changed direction.

Those heart cells release tiny sacs, called exosomes, that carry healing messages inside them. Ahmed Ibrahim, PhD, MPH, first author of the study, led the effort to decode those messages.

“Exosomes are like envelopes with important information,” Ibrahim said. “We wanted to take apart these coded messages and find which ones actually heal.”

Inside those sacs, the team found fragments of RNA. One stood out. It was small but powerful. In animals, it reduced heart damage after an attack. To use it as a drug, scientists rebuilt it in the lab and improved it. They trimmed it and toughened it so it would last longer in cells.

The finished version was called TY1.

TY1 does not act on the heart directly. It targets immune cells known as macrophages, which rush to injured areas after a heart attack. These cells can either help heal or make damage worse.

Inside macrophages, TY1 boosts a gene called TREX1. That gene makes an enzyme that clears damaged DNA. When broken DNA piles up, it triggers strong immune reactions. Clearing it calms the cell.

As TREX1 rises, inflammation falls. At the same time, cells release more of a soothing signal named interleukin-10, which helps tissues repair.

In man-made immune cells in the lab, TY1 shut down messages linked to stress and aging. It also reduced the buildup of misfolded proteins, another sign of cellular strain.

Safety came first. Healthy mice received TY1 for four weeks. Their blood tests stayed normal. Their organs showed no signs of harm.

Then came heart attack tests.

In rats, scientists briefly blocked blood flow to the heart and then restored it, like what happens in people who receive emergency care. Twenty minutes later, some animals received TY1. Others received a harmless placeholder.

Two days later, the results were clear. Rats given TY1 had smaller areas of heart damage. Their blood showed less troponin, a standard injury marker.

Weeks later, their hearts still worked better. Pumping strength rose. Chambers did not stretch as much. Scars were smaller.

A pig study followed. Because pigs have hearts closer in size to humans, they are seen as a key step before human trials. Again, TY1 reduced the size of heart injury.

Perhaps most striking, the drug worked even when given under the skin without special helpers. That suggests it may be easier to deliver in people.

To find where TY1 traveled, the team tagged it and followed its path. It reached many organs within minutes. Immune cells absorbed the most.

When scientists removed macrophages from rats before a heart attack, TY1 lost its effect. When they placed TY1-treated macrophages back into injured rats, the animals improved.

Those immune cells also released healing packages of their own. In dishes, these packages helped heart-like cells survive toxic stress.

In living rats, they also shrank heart injury. Blocking these packages erased the benefit.

This showed that TY1 reprograms macrophages. It turns them from fighters into rebuilders.

TY1 could reach beyond heart attacks. In other tests, it improved disease linked to heart stiffness and hardened skin conditions. Researchers believe it might help illnesses tied to DNA injury, including lupus and Duchenne muscular dystrophy.

“By probing the mechanisms of stem cell therapy, we discovered a way to heal the body without using stem cells,” Marbán said.

Ibrahim agrees. “By enhancing DNA repair, we can heal tissue damage that occurs during a heart attack,” he said. “This opens new options for many disorders.”

Human trials will come next.

For now, TY1 offers a rare kind of hope. It suggests that healing can begin not just with blood flow, but with fixing damage at the smallest level of life.

Research findings are available online in the journal Science Translational Medicine.

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