Research Hints at New Systemic Sclerosis Treatment

Investigators at Cedars-Sinai Health Sciences University used an experimental drug to reverse the effects of systemic sclerosis, a serious autoimmune disease. The study, conducted in a laboratory, was published in JCI Insight . Systemic sclerosis, also called scleroderma , is a chronic, life-threatening condition that scars the skin, lungs, heart and other organs. Because there is no cure or known cause for the disease, which affects about 100,000 people in the U.S., treatments focus on relieving symptoms. "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." Investigators tested the experimental drug, called TY1, on immune cells collected from patients with systemic sclerosis. They found that the drug reduced inflammation and DNA damage in those cells. When they administered TY1 to laboratory mice with a condition that mimics systemic sclerosis, investigators found that heart function and physical activity improved, and scar formation in organs was reduced. TY1, which was developed at Cedars-Sinai, is a synthetic version of a type of noncoding ribonucleic acid (RNA), a molecule that regulates cellular processes. After using TY1 to reduce tissue damage in laboratory experiments addressing heart attacks, as reported last year , investigators sought to determine if TY1 might have a similar effect on autoimmune disorders. "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," said Ahmed Ibrahim, PhD , associate professor of Cardiology at Cedars-Sinai and a co-investigator of the study. Investigators are currently preparing an investigational new drug application to the U.S. Food and Drug Administration, the first step toward obtaining approval for studying TY1 in people with systemic sclerosis. "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. Additional Cedars-Sinai authors include Salwa Soussi, Alessandra Ciullo, Kara Tsi, Weixin Liu, Liang Li, Mario Fournier, Thassio Mesquita, Alberto Marchevsky, Nunzio Bottini and Francesco Boin. Xaviar Jones, MD, is the first author of the paper and is currently completing his residency training at Yale University. Funding: This work is the result of National Institutes of Health funding, in whole or in part, and is subject to the NIH Public Access Policy. Through acceptance of this federal funding, the NIH has been given a right to make the work publicly available in PubMed Central. Supported funding for this study include grants NIH (R01HL164588 to EM, and T32HL116273 to EM, which supported XMJ), and the California Institute for Regenerative Medicine (TRAN1-15317 to AGI). Disclosures: EM owns founder's equity in Capricor. AI owns stock in Capricor. Capricor has no relationship with this project, nor any licensing rights to the discoveries reported here. All other authors declare no competing interests. Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.