Molecular magnetic resonance imaging accurately measures the antifibrotic effect of EDP‐305, a novel farnesoid X receptor agonist

• DOI: 10.1002/hep4.1193
• Publication Date: 2018-05-21T12:55:08Z
• Authors: Derek J. Erstad; Christian T. Farrar; Sarani Ghoshal; Ricard Masia; Diego S. Ferreira; Yin‐Ching Iris Chen; Ji‐Kyung Choi; Lan Wei; Phillip A. Waghorn; Nicholas J. Rotile; Chuantao Tu; Katherine A. Grah...; Mozhdeh Sojoodi; Shen Li; Yang Li; Guogiang Wang; Kathleen E. Corey; Yat Sun Or; Lijuan Jiang; Kenneth K. Tanabe; Peter Caravan; Bryan C. Fuchs
• Keywords: Hydroxyproline; Farnesoid X receptor; Hepatic fibrosis

We examined a novel farnesoid X receptor agonist, EDP‐305, for its antifibrotic effect in bile duct ligation (BDL) and choline‐deficient, L‐amino acid‐defined, high‐fat diet (CDAHFD) models of hepatic injury. used molecular magnetic resonance imaging with the type 1 collagen‐binding probe EP‐3533 oxidized collagen‐specific gadolinium hydrazide to noninvasively measure treatment response. BDL rats (n = 8 each group) were treated either low or high doses EDP‐305 starting on day 4 after imaged 18. CDAHFD mice at 6 weeks 12 weeks. Liver tissue was subjected pathologic morphometric scoring fibrosis, hydroxyproline quantitation, determination fibrogenic messenger RNA expression. High‐dose (30 mg/kg) reduced liver fibrosis both as measured by collagen proportional area, analysis, gene expression (all P < 0.05). Magnetic signal intensity model 30 mg/kg ( 0.01). Histologically, halted progression model. Conclusion : rat mouse models. Molecular is sensitive changes could be response clinical trials. Hepatology Communications 2018;2:821‐835)