Investigators at Cedars-Sinai Health Sciences University report that an experimental drug, TY1, reduced scarring and improved organ function in a laboratory model of systemic sclerosis, a chronic autoimmune disease. The findings, published in JCI Insight, suggest TY1 could become a future therapy for a condition affecting roughly 100,000 people in the U.S.
Systemic sclerosis, also known as scleroderma, causes progressive fibrosis of the skin and internal organs including the lungs, heart and kidneys. The disease has no known cause or cure, so current treatments focus on symptom management.
“That’s why we are so excited about our findings,” said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute at Cedars-Sinai and corresponding author of the study. “The basic immune system pathway driving systemic sclerosis is blocked by this new drug, making it a potential future therapy.”
The research team tested TY1 on immune cells from patients with systemic sclerosis and found the drug reduced inflammation and DNA damage in those cells.
When administered to laboratory mice with a condition mimicking the disease, TY1 improved heart function, increased physical activity and decreased organ scarring.
TY1 is a synthetic version of a noncoding ribonucleic acid (RNA) molecule that regulates cellular processes. The drug was developed at Cedars-Sinai following earlier studies showing it reduced tissue damage in models of heart attacks, as reported last year.
The team chose to test TY1 in systemic sclerosis because the drug’s mechanism of action aligns with the disease’s pathology and because the condition represents a significant unmet medical need, said Ahmed Ibrahim, PhD, associate professor of Cardiology at Cedars-Sinai and a co-investigator on the study.
According to Susan Cheng, MD, chair of the Department of Cardiology in the Smidt Heart Institute, the innovative study demonstrates how doing careful research on one disease can lead to key discoveries on another, such as 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.
The research team included Jones XM, Soussi S, Ciullo A, Tsi K, Liu W, Li L, Fournier M, Mesquita T, Marchevsky AM, Bottini N, Boin F, Ibrahim AG, Marbán E. Their study was titled “Noncoding RNA TY1 reverses fibrosis in systemic sclerosis by attenuating the cGAS/STING pathway.”
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