Ardizzone Sandro, Bevivino Gerolamo, Monteleone Giovanni
Gastroenterology Unit, Department of Biomedical and Clinical Sciences, 'Luigi Sacco' University Hospital, 20157 Milano, Italy.
Department of Systems Medicine, University of Rome 'Tor Vergata', Via Montpellier, 1, 00133 Rome, Italy.
Therap Adv Gastroenterol. 2016 Jul;9(4):527-32. doi: 10.1177/1756283X16636781. Epub 2016 Mar 15.
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.
在克罗恩病（CD）中，组织损伤性炎症是由反调节机制缺陷所维持的，这种机制通常会抑制免疫炎症信号并促进黏膜损伤的修复。特别是，在CD患者的炎症肠道中，Smad7水平升高，Smad7是一种抑制转化生长因子（TGF）-β1功能的细胞内蛋白。用一种名为蒙氏寡核苷酸（mongersen）的特异性反义寡核苷酸敲低Smad7，可恢复TGF-β1活性，从而抑制炎症途径并使小鼠结肠炎消退。同样，对活动性CD患者口服蒙氏寡核苷酸可诱导临床缓解。在本文中，我们回顾了支持Smad7在CD中致病作用的现有数据，并讨论了近期评估蒙氏寡核苷酸在CD患者中疗效和安全性的I期和II期试验结果。
