title: Mongersen, an oral Smad7 antisense oligonucleotide, in patients with active Crohn's disease.
abstract: In Crohn's disease (CD), the tissue-damaging inflammation is sustained by defects of counter-regulatory mechanisms, which normally inhibit immune-inflammatory signals and promote repair of mucosal injury. In particular, in inflamed gut of CD patients there are elevated levels of Smad7, an intracellular protein that inhibits the function of transforming growth factor (TGF)-β1. Knockdown of Smad7 with a specific antisense oligonucleotide, named mongersen, restores TGF-β1 activity thus leading to suppression of inflammatory pathways and resolution of colitis in mice. Consistently, oral administration of mongersen to patients with active CD induces clinical remission. In this article, we review the available data supporting the pathogenic role of Smad7 in CD and discuss the results of recent phase I and II trials assessing the efficacy and safety of mongersen in CD patients.
authors.affiliation: Gastroenterology Unit, Department of Biomedical and Clinical Sciences, 'Luigi Sacco' University Hospital, 20157 Milano, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Ardizzone
authors.affiliation: Department of Systems Medicine, University of Rome 'Tor Vergata', Via Montpellier, 1, 00133 Rome, Italy.
authors.forename: Gerolamo
authors.initials: G
authors.lastname: Bevivino
authors.affiliation: Department of Systems Medicine, University of Rome `Tor Vergata', Via Montpellier, 1, 00133 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
keywords: IBD; Smad7; TGF-β; colitis; mucosal immunity