A new paper published in Science Translational Medicine describes an experimental drug capable of repairing DNA damage caused by disease. Developed by scientists at Cedars-Sinai, the potential treatment is a prototype for a new class of medications that fix tissue damage caused by heart attacks, inflammatory disease, and other conditions. Details of the drug, dubbed TY1, can be found in the paper titled “Augmentation of DNA exonuclease TREX1 in macrophages as a therapy for cardiac ischemic injury.”
According to its developers, TY1 is a laboratory-made version of an RNA molecule that naturally exists in the body. It works by enhancing the action of a gene called TREX1, which helps immune cells clear damaged DNA, and supports tissue repair. It is the “first exomer—a new class of drugs that address tissue damage in unexpected ways,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and the study’s senior author. “By probing the mechanisms of stem cell therapy, we discovered a way to heal the body without using stem cells.”
The studies that led to TY1’s development have been going on for more than two decades. Marbán’s previous lab at Johns Hopkins University worked on a technique for isolating progenitor cells from the human heart. Building on that work at Cedars-Sinai, Marbán’s team discovered that these heart progenitor cells send out exosomes loaded with RNA molecules that help repair and regenerate injured tissue.
The scientists aimed to elucidate the nature of the RNA molecules. “Exosomes are like envelopes with important information,” said Ahmed Ibrahim, PhD, an associate professor in the cardiology department at 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.”
To get those answers, the scientists sequenced the RNA material inside the exosomes. One RNA molecule proved to be more abundant than others, suggesting that it might be important for tissue healing. In fact, the molecule proved effective in promoting healing after heart attacks in laboratory animals.
TY1 is a synthetic, engineered version of that RNA molecule, designed in a way that mimics the structure of approved RNA drugs already in clinical use. It works by upping the production of immune cells that reverse DNA damage. This process minimizes the formation of scar tissue after a heart attack.
“We are particularly excited because TY1 also works in other conditions, including autoimmune diseases that cause the body to mistakenly attack healthy tissue,” Ibrahim said. “This is an entirely new mechanism for tissue healing, opening new options for a variety of disorders.”
The next step is to study TY1 in clinical trials.
