LIMR researchers uncover potential new therapy for ulcerative colitis

Researchers at the Lankenau Institute for Medical Research (LIMR) have isolated an antibody that may offer a new strategy to treat ulcerative colitis (UC).

UC affects about 907,000 Americans, according to the Crohn’s and Colitis Foundation of America. The disease can cause abdominal pain, weight loss, fatigue and frequent diarrhea, among other symptoms. Additionally, patients with UC are at an increased risk of developing colorectal cancer, due in part to disease-causing inflammation of colon tissues.

Patients with UC currently are prescribed anti-inflammatory drugs and immune suppressors whose unpleasant side effects, such as opportunistic infections and lack of efficacy in certain individuals, limit treatment quality.

LIMR researchers and their colleagues determined in preclinical studies that injection of an antibody against Bin1, a protein that promotes inflammation by loosening tissue integrity, can trigger an immunotherapeutic benefit to prevent and treat UC.

“We found that administration of a Bin1 monoclonal antibody improved the colon’s cellular barrier function and protected the integrity of the lymphoid follicles in the colon,” noted Sunil Thomas, PhD, research assistant professor at LIMR and lead author of the study. “The antibody appeared to lower the expression of several cytokines, inflammatory agents in the cells, and thus protected the animals in our study from developing UC.”

The study advanced earlier genetics research at LIMR revealing that shutting off the Bin1 gene in mice reduced UC severity and did so by boosting the barrier function of the epithelium, the lining of the colon. Based on the results of that study, the researchers then developed a Bin1 monoclonal antibody treatment for preclinical administration.

“We found that the Bin1 antibody affected the expression of various claudin proteins in the tight junction complexes, and thereby the barrier function of the epithelium,” said LIMR Professor James Mullin, PhD, one of the study’s authors. “Enhancing the tight junctional complexes may prove to be protective regarding the development of UC.”

The authors concluded that the study offers both a potential new immunotherapy for UC and shows that multiple factors may be involved in UC development. Their study, “Intestinal barrier tightening by a cell-penetrating antibody to Bin1, a candidate target for immunotherapy of ulcerative colitis,” was published in the Journal of Cellular Biochemistry and is available here:

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.27716.

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