Crohn’s & Colitis Congress™

Sessions Speakers Exhibitors Floor Plan Buzz

P032 - EPICERTIN ENHANCES INTESTINAL WOUND HEALING IN A MOUSE COLITIS MODEL AND HUMAN ULCERATIVE COLITIS COLON EXPLANTS (Room Poster Hall)

Epicertin (EPT) is a new ulcerative colitis (UC) drug candidate derived from the nontoxic component of Vibrio cholerae cholera toxin. We have recently shown that oral administration of EPT in mice induces mucosal healing in the colon mediated by transforming growth factor (TGFβ). Here, we investigate EPT’s mucosal healing mechanism and its therapeutic potential in in vitro, in vivo, and ex vivo models. Methods: In a human colon epithelial cell (Caco2) wound healing model, wound closure and cytokine/gene expression after 24-hour treatment was measured. Effects of topically administered EPT were tested in dextran sulfate sodium (DSS) models of acute and chronic colitis in C57BL/6J mice. Body weights and fecal samples were examined for a Disease Activity Index (DAI). Colons were analyzed for cytokine/gene expression and histopathological scoring. UC colon explants were obtained from consenting patients who underwent total colectomy, which were cultured with EPT or vehicle control for 24 hours and analyzed for wound healing-related gene expression using RT-qPCR. Results: In the Caco2 model, EPT significantly enhanced wound repair in a TGFβ-dependent manner. Gene expression analysis suggested that an unfolded protein response (UPR) plays a significant role in the wound healing activity. In a DSS acute colitis mouse model, oral and rectal administration of EPT significantly facilitated recovery from colon mucosal damage. In the chronic colitis model, biweekly EPT oral administration significantly reduced chronic inflammation and azoxymethane-induced tumorigenesis. Furthermore, EPT induced a mild UPR and a strong wound healing response in human UC colon explants. These results suggest that EPT induces colon epithelial wound healing via the activation of UPR and strongly support the development of EPT as a topical biotherapeutic for UC. As current therapeutic options can achieve mucosal healing in only ~50% of patients, EPT may address an unmet need in UC treatment.