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Peter Mannon, MD |
Peter Mannon, MD, professor of medicine and chief of the UNMC Division of Gastroenterology and Hepatology, is co-author of a paper about a recent study that may hold promise in providing long-term remission of Crohn’s disease, one type of inflammatory bowel disease.
“We’re pretty good at controlling acute flares of the disease, but not so good at preventing recurrent flares. That would be the holy grail of treating this disease — maintaining remission,” Dr. Mannon said. “We have a potential new approach to treating Crohn’s disease that specifically targets a cell or group of cells to eliminate the source inflammation without causing general immunosuppression. This would represent a radically new way to achieve long-term remission.”
Details about the study are published Dec. 11 in the high-profile journal, Science Immunology.
“The unique thing about Crohn’s is patients have abnormal immune responses to the usual bacteria living in the intestines, which causes them to make antibodies against what’s called flagellin-proteins that aren’t seen in healthy controls or ulcerative colitis,” said Dr. Mannon, who also serves as director of the Frederic F. Paustian Inflammatory Bowel Disease Center at UNMC. “If the abnormal immune memory contained in these cells could be eliminated, then they would not be present to cause disease over and over.”
The research team wanted to know if blocking the immune response of just these flagellin-responsive T cells alone would help improve or prevent inflammation that causes Crohn’s disease.
The team focused on mouse models with Crohn’s-like inflammation as well as donated blood from patients. They created artificial proteins made from flagellin proteins and introduced them in mice, which caused CD4 T cells to become activated and produce inflammatory signals.
“We showed if we took the T-cells that recognized flagellin proteins and pre-treated them with the drugs metformin and rapamycin (already approved for use in humans) while being activated, that they could block activation and growth and induce cell death and get rid of them,” Dr. Mannon said. “The important message is we can target T cells that are active in Crohn’s disease while maintaining normal immunity.
“We found T cells play a central role in Crohn’s disease, which had been controversial. Our findings support moving this line of investigation into human trials aimed at selective ablation of memory T cells causing Crohn’s disease.”
The study funding was provided by the Crohn’s & Colitis Foundation and the National Institutes of Health.