Researchers Discover That Protein Produced in Gut Could Stave Off Life-Threatening Side Effect in Bone Marrow Transplants
Findings Could Lead to New Treatments for Inflammatory Bowel Disease, Other GI Illnesses
Researchers at Mount Sinai have discovered that an antimicrobial protein found in the gut can stave off a common and highly lethal side effect of bone marrow transplants, according to a study published in the Journal of Clinical Investigation in September.
The protein, regenerating islet-derived 3-alpha (REG3α), is made by cells in the lining of the gastrointestinal tract. It plays a role in a complication of bone marrow transplants called graft-versus-host-disease (GVHD), in which the donated bone marrow’s immune cells attack the patient’s gastrointestinal tract.
This study shows that GVHD causes increased serum levels of REG3α throughout the body while, paradoxically, decreasing the production of the protein in the gastrointestinal tract as GVHD worsens.
The Mount Sinai researchers showed that mice that could not make the protein did not survive GVHD, but also found that adding REG3α to human gastrointestinal cell lines prolonged their survival, confirming its unexpected function. These findings demonstrated that REG3α, previously only considered a biomarker for GVHD, can have a role in saving patients from the disease.
While patients suffering from GVHD are normally given immune suppressants, this research suggested that enhancing the immune system with REG3α is a better strategy and may also be helpful for illnesses such as inflammatory bowel disease that also involve the immune system in the gastrointestinal tract.
“There is a way to treat immune disorders of the gastrointestinal tract by enhancing the immune system rather than suppressing it, as we do now,” said lead researcher James Ferrara, MD, Ward-Coleman Chair of Cancer Medicine and Director of the Hematologic Malignancies Translational Research Center at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai and Co-Director of the Mount Sinai Acute GVHD International Consortium (MAGIC). “These results show a new function for the lining of the gastrointestinal tract protecting itself, leading to a new class of drugs.”
CLICK HERE for a video of Dr. Ferrera talking about the research.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology and the South Nassau Communities Hospital is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.