TY1: new experimental drug restores tissue after heart attack

Cedars-Sinai researchers have created an experimental drug, named TY1, that repairs DNA and represents a prototype for a new class of medications aimed at fixing tissue damage caused by heart attacks, inflammatory diseases and other conditions.

A new approach to healing

“By probing the mechanisms of stem cell therapy, we discovered a way to heal the body without using stem cells,” said Dr Eduardo Marbán, MD, executive director of the Smidt Heart Institute at Cedars-Sinai and the study’s senior author. “TY1 is the first exomer – a new class of drugs that address tissue damage in unexpected ways.”

TY1 is a laboratory-made version of an RNA molecule naturally present in the body. The research team demonstrated that TY1 enhances the activity of a gene called TREX1, which enables immune cells to clear damaged DNA. This process then promotes the repair of injured tissue.

Two decades of research

The development of TY1 is the culmination of more than 20 years of research. The project began when Marbán’s previous laboratory at Johns Hopkins University developed a method to isolate progenitor cells from the human heart. Like stem cells, progenitor cells can transform into new, healthy tissue, but they do so in a more targeted way. Heart progenitor cells, for example, can promote regeneration of damaged cardiac tissue.

Like stem cells, progenitor cells can transform into new, healthy tissue, but they do so in a more targeted way.

At Marbán’s current laboratory at Cedars-Sinai, Dr Ahmed Ibrahim, MPH, discovered that these heart progenitor cells release tiny molecule-filled sacs known as exosomes. These sacs carry RNA molecules that play a role in repairing and regenerating injured tissue.

“Exosomes are like envelopes with important information,” said Ibrahim, who is associate professor in the Department of Cardiology in the Smidt Heart Institute and first author of the paper. “We wanted to take apart these coded messages and figure out which molecules were, themselves, therapeutic.”

From RNA discovery to synthetic drug

Scientists sequenced the RNA material inside the exosomes and found one RNA molecule to be more abundant than the others, suggesting a key role in tissue healing. Laboratory tests showed that the natural RNA molecule effectively promoted healing after heart attacks in animals. TY1 is the engineered, synthetic version of this RNA molecule, made to mirror the structure of RNA drugs already approved for clinical use.

Scientists sequenced the RNA material inside the exosomes and found one RNA molecule to be more abundant than the others, suggesting a key role in tissue healing.

TY1 functions by increasing the production of immune cells that reverse DNA damage, thereby reducing scar tissue formation following a heart attack.

“By enhancing DNA repair, we can heal tissue damage that occurs during a heart attack,” Ibrahim said. “We are particularly excited because TY1 also works in other conditions, including autoimmune diseases that cause the body to mistakenly attack healthy tissue. This is an entirely new mechanism for tissue healing, opening up new options for a variety of disorders.”

Next steps

The research team now plans to test TY1 in clinical trials, marking a significant step towards the development of new regenerative medicines and RNA-based therapies.