Preclinical validation of oral therapeutic lead proteins targeting epithelial GM1 ganglioside for ulcerative colitis therapy

The goal of the current subcontract is to determine the efficacy of CTBSEKDEL in a chronic model of colitis. Studies performed at the University of Kentucky will test a dose range of CTBSEKDEL given to IL-10 KO mice after they were induced with a two week course of piroxicam as published (DAYS 0 – 14)(1, 2). Treatment will be administered (range of three doses) after the induction of colitis (DAY 14-28) to mimic human therapy. Treatment effect will be measured at DAY 28 using clinical parameters as described in the research plan (weight loss, diarrhea severity, colonic bleeding, etc), and tissue markers of inflammation (mRNA and protein for chemokine and cytokine as published (4)) and via histology as below (3).