Cooperative Laboratory CNRS-Montpellier University, Montpellier, France; ABIVAX, 1919 Route de Mende, 34293 Montpellier, France.
Cooperative Laboratory CNRS-Montpellier University, Montpellier, France.
Drug Discov Today. 2021 Apr;26(4):1030-1039. doi: 10.1016/j.drudis.2020.12.019. Epub 2020 Dec 30.
Inflammatory diseases are believed to develop as a result of dysregulated inflammatory responses to environmental factors on susceptible genetic backgrounds. Operating at the level of post-transcriptional gene regulation, miRNAs are a class of endogenous, small noncoding RNAs that can promote downregulation of protein expression by translational repression and/or mRNA degradation of target mRNAs involved in inflammation. MiR-124 is a crucial modulator of inflammation and innate immunity that could provide therapeutic restitution of physiological pathways lost in inflammatory diseases. A recently discovered small quinoline, ABX464, was shown to upregulate miR-124 in human immune cells. In vivo, in a proof-of-concept clinical study, ABX464 showed robust and consistent efficacy in ulcerative colitis (UC). In this review, we examine the current therapeutic options proposed for UC and discuss the drug candidate ABX464 in this context.
炎症性疾病被认为是由于易感遗传背景下对环境因素的炎症反应失调而发展起来的。miRNAs 作为一类内源性的小非编码 RNA，在转录后基因调控水平上发挥作用，可通过翻译抑制和/或参与炎症的靶 mRNA 的降解来促进蛋白质表达的下调。miR-124 是炎症和先天免疫的关键调节因子，它可以为炎症性疾病中丧失的生理途径提供治疗恢复。最近发现的一种小分子喹啉 ABX464 被证明可以在人类免疫细胞中上调 miR-124。在体内，在一项概念验证性临床研究中，ABX464 在溃疡性结肠炎（UC）中表现出强大而一致的疗效。在这篇综述中，我们检查了目前为 UC 提出的治疗选择，并在这一背景下讨论了候选药物 ABX464。
