Neurotherapeutics

, Volume 14, Issue 1, pp 191–198

A Novel Fusion Protein, AChR-Fc, Ameliorates Myasthenia Gravis by Neutralizing Antiacetylcholine Receptor Antibodies and Suppressing Acetylcholine Receptor-Reactive B Cells

  • Masayuki Homma
  • Akiyuki Uzawa
  • Hitoshi Tanaka
  • Naoki Kawaguchi
  • Tetsuya Kanai
  • Kenji Nakajima
  • Masakuni Narita
  • Yukio Hara
  • Hideya Maruyama
  • Yasumasa Ogawa
  • Keiichi Himuro
  • Satoshi Kuwabara
Original Article

DOI: 10.1007/s13311-016-0476-9

Cite this article as:
Homma, M., Uzawa, A., Tanaka, H. et al. Neurotherapeutics (2017) 14: 191. doi:10.1007/s13311-016-0476-9

Abstract

Most patients with myasthenia gravis (MG) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, which leads to muscle weakness. We developed a fusion protein, AChR-Fc, as a novel therapeutic biomolecule for patients with MG and examined its efficacy. AChR-Fc was expressed by Chinese hamster ovary cells and purified. We examined the neutralizing activity and cellular cytotoxicity of AChR-Fc using anti-AChR antibody-producing hybridoma cells and serum samples from 16 patients with MG. The effects of AChR-Fc in vivo were also examined using rat MG models. AChR-Fc bound to anti-AChR antibodies and exhibited cytotoxicity against patient-derived antibody-producing B cells. Additionally, a dose-dependent improvement in the clinical signs of disease was observed in a rat MG model. AChR-Fc can diminish signs of MG by neutralizing anti-AChR antibodies and enhancing cytotoxicity against autoantibody-producing B cells. Thus, AChR-Fc can be a novel therapeutic biomolecule for patients with MG.

Keywords

AChR-Fc Myasthenia gravis Anti-AChR antibody Neutralization ADCC 

Supplementary material

13311_2016_476_MOESM1_ESM.pdf (1.2 mb)
ESM 1(PDF 1224 kb)

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2016

Authors and Affiliations

  • Masayuki Homma
    • 1
  • Akiyuki Uzawa
    • 2
  • Hitoshi Tanaka
    • 1
  • Naoki Kawaguchi
    • 2
  • Tetsuya Kanai
    • 2
  • Kenji Nakajima
    • 1
  • Masakuni Narita
    • 1
  • Yukio Hara
    • 1
  • Hideya Maruyama
    • 1
  • Yasumasa Ogawa
    • 1
  • Keiichi Himuro
    • 2
  • Satoshi Kuwabara
    • 2
  1. 1.Research LaboratoryNihon Pharmaceutical Co. Ltd.ChibaJapan
  2. 2.Department of Neurology, Graduate School of MedicineChiba UniversityChibaJapan