Preclinical development of epicertin, a novel biotherapeutic for the treatment of ulcerative colitis.
Date on Master's Thesis/Doctoral Dissertation
Pharmacology and Toxicology
Pharmacology and Toxicology, MS
Committee Co-Chair (if applicable)
Epicertin (EPT) is a recombinant variant of the cholera toxin B subunit with a C-terminal KDEL endoplasmic retention motif. Previously, orally administered EPT demonstrated mucosal healing activity in acute and chronic dextran sulfate sodium colitis models, indicating its therapeutic potential for ulcerative colitis (UC) treatment. However, oral dosing with EPT requires neutralization of gastric acid prior to administration, hindering its facile application in the treatment of chronic diseases like UC. One solution to this issue is that EPT may also be administered intracolonically without losing efficacy. This work describes the determination of a target intracolonic dose of EPT for future first-in-human safety trials as well as the development of a prototype oral formulation of EPT that prevents stomach acid degradation for pH-dependent release at the colon.
Reeves, Micaela Ann, "Preclinical development of epicertin, a novel biotherapeutic for the treatment of ulcerative colitis." (2021). Electronic Theses and Dissertations. Paper 3615.