An experimental synthetic RNA drug has shown promise in repairing damaged hearts after attacks by targeting immune cells to fix broken DNA and curb inflammation, potentially reducing scarring and improving recovery, according to a new study.
Researchers at Cedars-Sinai Medical Center developed the drug, dubbed TY1, which they describe as the inaugural member of a novel class called exomers. The findings, detailed in Science Translational Medicine, stem from over two decades of work starting at Johns Hopkins University, where scientists first isolated heart progenitor cells that release healing exosomes — tiny sacs carrying RNA fragments.
“Exosomes are like envelopes with important information,” Ahmed Ibrahim, the study’s first author and a researcher at Cedars-Sinai, said, per the Brighter Side of News. “We wanted to take apart these coded messages and find which ones actually heal.”
The team identified a potent RNA snippet, then engineered TY1 by shortening and stabilizing it for longer cellular activity. Rather than acting directly on heart tissue, TY1 influences macrophages, immune cells that can exacerbate or aid healing after an attack.
It elevates the TREX1 gene, producing an enzyme that eliminates the buildup of damaged DNA, which otherwise fuels intense immune responses. This dampens inflammation while ramping up interleukin-10, a signal promoting tissue repair.
In lab-grown immune cells, TY1 suppressed stress- and aging-associated signals and reduced misfolded protein accumulation.
“TY1 is the first exomer, a new class of drugs that address tissue damage in unexpected ways,” said Eduardo Marbán, Cedars-Sinai’s executive director and a study co-author, per Brighter Side.
Initial safety tests in healthy mice over four weeks revealed no abnormalities in blood or organs. In rats mimicking human heart attacks — with temporary blood flow blockage followed by restoration — TY1, administered 20 minutes later, reduced infarct size, lowered troponin levels, improved pumping function, limited chamber stretching, and minimized scar formation weeks later.
Similar benefits were observed in pigs, whose hearts more closely resemble human hearts, with reduced injury even with a simple under-the-skin injection.
Tracking tagged TY1 showed it was quickly distributed to organs, with heavy uptake by immune cells. Eliminating macrophages in rats abrogated their effects, whereas reintroducing TY1-treated macrophages improved outcomes. These reprogrammed cells also secreted their own healing exosomes, which protected heart-like cells from stress in lab dishes and shrank injuries in live rats; blocking the exosomes erased the gains.
Beyond cardiac events, TY1 aided conditions involving heart stiffness and skin hardening, hinting at applications in DNA-damage-linked disorders such as 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 added, “By enhancing DNA repair, we can heal tissue damage that occurs during a heart attack. This opens new options for many disorders.”
Human trials are planned next.