Research Project
8833074
? DESCRIPTION (provided by applicant): Glucocorticoids (e.g. prednisolone) are prescribed frequently to treat inflammatory bowel disease (IBD). Despite effectiveness, adverse side effects believed to be caused by GRE-mediated transcriptional properties limit long term use of glucocorticoids in IBD patients. Furthermore, these GRE-mediated transcriptional activities have been previously shown to be responsible for glucocorticoid-induced impaired healing of the intestinal epithelium. This may explain why glucocorticoids do not appear to be effective in maintaining remission of disease. ReveraGen BioPharma has identified a novel dissociative steroidal compound (VBP15) designed that retains the anti-inflammatory efficacy of traditional steroids (via NFkB inhibition), but has lost GRE-mediated transcriptional activities. VBP15 treatment has been shown to reduce inflammatory activity in vivo in multiple models of disease including the TNBS-induced mouse model of colitis (preliminary data) and result in a much milder side effect profile. Furthermore, in preliminary studies utilizing the epithelial injury- induced dextran sodium sulfate mouse model of colitis, VBP15, in contrary to prednisolone, reduced disease severity suggesting that VBP15 may possess a more benign effect on the restitution processes of the injured intestinal epithelium. Therefore, VBP15 may represent a more effective, yet safer alternative to traditional glucocorticoids in the long-term treatment of IBD. The goal of this STTR proposal is to demonstrate that VBP15, unlike conventional glucocorticoids, does not impair the restitution of injured intestinal epithelium both in vitro andin vivo. Thus, identification of a compound that inhibits pro-inflammatory activity and also does not impair efficient restitution of the intestinal epithelium may represent a therapeutic that possibly alters the natural history of inflammatory bowel disease.
