A synthetic noncoding RNA molecule called TY1 has demonstrated potential for reversing damage in systemic sclerosis, an autoimmune disease without a known cure. Findings from Cedars-Sinai Health Sciences University, published in JCI Insight, reveal that TY1 reduces inflammation and DNA damage in immune cells from affected patients. The disease, also known as scleroderma, impacts roughly 100,000 people in the U.S. and causes scarring in the skin, lungs, heart, and other organs. Current treatments focus solely on symptom management, as the underlying cause remains unclear.
Researchers tested TY1 on immune cells collected from patients with systemic sclerosis and on laboratory mice with a condition that mimics the disease. They found improved heart function, reduced organ scarring, and enhanced physical activity in treated subjects. The drug was developed at Cedars-Sinai following earlier work that limited tissue damage from heart attacks. It operates by blocking the cGAS/STING pathway, a critical immune system pathway linked to fibrosis in systemic sclerosis. “The basic immune system pathway driving systemic sclerosis is blocked by this new drug, making it a potential future therapy,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and lead author.
The team is now preparing an investigational new drug application for the U.S. Food and Drug Administration, marking the first step toward human trials. This study builds on previous research showing TY1’s ability to address fibrosis across different conditions, indicating broader applications for treating chronic scarring diseases. “This innovative study illustrates how doing careful research on one disease can lead to key discoveries on another—in this case, from conditions that can stiffen the heart to scleroderma, a rare disease that hardens the skin and internal organs in patients who have waited decades for better treatment options,” said Susan Cheng, MD, chair of the Department of Cardiology in the Smidt Heart Institute.
Systemic sclerosis has long lacked effective treatments, leaving patients with few options to slow progression. Ahmed Ibrahim, PhD, associate professor of Cardiology at Cedars-Sinai and a co-investigator of the study, highlighted the drug’s logical alignment with the disease. “We chose to test TY1 in systemic sclerosis because the science of how the drug works makes sense and also because it is such a devastating disease,” he said. The researchers plan to expand testing to assess safety and efficacy before seeking regulatory approval.
