Inhibition of RGMa alleviates symptoms in a rat model of neuromyelitis optica

Kana Harada,Hideki Mochizuki,Toshihide Yamashita,Shogo Tanabe,Tatsusada Okuno,Yuki Fujita,Yoshihisa Koyama

doi:10.1038/s41598-017-18362-2

Kana Harada, Hideki Mochizuki + Show 5 more

Open Access

https://doi.org/10.1038/s41598-017-18362-2

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Journal: Scientific Reports	Publication Date: Jan 8, 2018
Citations: 18	License type: open-access

Affiliation: Osaka University

Abstract

Neuromyelitis optica (NMO) is an autoimmune disease associated with NMO immunoglobulin G (NMO-IgG), an antibody that selectively binds to the aquaporin-4. Here, we established a localized NMO model by injecting NMO-IgG into the spinal cord, and assessed the efficacy of treating its NMO-like symptoms by blocking repulsive guidance molecule-a (RGMa), an axon growth inhibitor. The model showed pathological features consistent with NMO. Systemic administration of humanized monoclonal anti-RGMa antibody delayed the onset and attenuated the severity of clinical symptoms. Further, it preserved astrocytes and reduced inflammatory-cell infiltration and axonal damage, suggesting that targeting RGMa is effective in treating NMO.

Highlights

Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system (CNS) characterized by inflammatory lesions in the spinal cord and optic nerve, which can lead to acute transverse myelitis[1]
Quantification analysis revealed that signal intensity of AQP4 and glial fibrillary acidic protein (GFAP) double-positive area was increased in NMO rats receiving anti-repulsive guidance molecule-a (RGMa) monoclonal antibody (mAb) treatment compared with Control-immunoglobulin G (IgG)-treated NMO rats (Fig. 2J,K)
Our rat model of NMO had no obvious loss of myelin basic protein (MBP)-immunofluorescence when compared to intact rats (Fig. 2L). This observation is consistent with the findings of a previous study[18]. These results suggest that anti-RGMa mAb treatment prevents the loss of astrocytes in the spinal cord, which corresponds to the delay and attenuated clinical symptoms observed in the NMO-model rats

Summary

Introduction

Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system (CNS) characterized by inflammatory lesions in the spinal cord and optic nerve, which can lead to acute transverse myelitis[1]. (G–I) Average onset day (G) and average maximum clinical score (H) for NMO model rats given Control IgG or anti-RGMa Ab. Clinical disease score in NMO-IgG injected rats treated with either Control-IgG or anti-RGMa Ab (I).

Results

Conclusion