Specific and selective induction of miR-124 in immune cells by the quinoline ABX464: a transformative therapy for inflammatory diseases

Drug Discov Today. 2021 Apr;26(4):1030-1039. doi: 10.1016/j.drudis.2020.12.019. Epub 2020 Dec 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Colitis, Ulcerative* / immunology
  • Colitis, Ulcerative* / therapy
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunologic Factors / pharmacology
  • Inflammation / drug therapy
  • Inflammation / genetics
  • MicroRNAs / immunology*
  • Quinolines / pharmacology*

Substances

  • ABX464
  • Immunologic Factors
  • MIRN124 microRNA, human
  • MicroRNAs
  • Quinolines