Targeting interleukin-6 to treat neuromyelitis optica spectrum disorders: Implications from immunology, the FcRn pathway and clinical experience

Drug Discov Today. 2021 Jul;26(7):1591-1601. doi: 10.1016/j.drudis.2021.03.018. Epub 2021 Mar 27.

Abstract

Neuromyelitis optica spectrum disorder (NMOSD) is a rare disease of the central nervous system (CNS) that is associated with poor outcomes for patients. Until recently, when complement inhibitors were approved, there was no approved therapy. Most recently, clinical trials of interleukin-6 (IL-6) blockade showed a therapeutic benefit for NMOSD. In this review, we introduce the immunological basis of IL-6 blockade in NMOSD and summarize current knowledge about the clinical use of the IL-6 receptor inhibitors tocilizumab and satralizumab. The aim of extending the half-life of monoclonal antibodies (mAbs) has been actualized by successful clinical translation for Satralizumab, achieved via the neonatal Fc receptor (FcRn) pathway. The basic principles of FcRn are highlighted in this review together with the potential therapeutic benefits of this emerging technology.

Keywords: Aquaporin antibody; Disease-modifying therapy; Interleukin-6; Monoclonal antibody; NMOSD; Neonatal pathway; Neuromyelitis optica.

Publication types

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

MeSH terms

  • Animals
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / immunology
  • Neuromyelitis Optica / drug therapy*
  • Neuromyelitis Optica / immunology
  • Receptors, Fc / immunology*
  • Signal Transduction

Substances

  • Histocompatibility Antigens Class I
  • Interleukin-6
  • Receptors, Fc
  • Fc receptor, neonatal