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Sci Rep. 2018 Jan 8;8(1):34. doi: 10.1038/s41598-017-18362-2.

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

Author information

1
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
2
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. yuki-fujita@molneu.med.osaka-u.ac.jp.
3
WPI Immunology Frontier Research Center, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. yuki-fujita@molneu.med.osaka-u.ac.jp.
4
Department of Immunopathology, Research Institute for Microbial Diseases, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
5
Department of Neurology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
6
WPI Immunology Frontier Research Center, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
7
Department of Neuroscience and Cell Biology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
8
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. yamashita@molneu.med.osaka-u.ac.jp.
9
WPI Immunology Frontier Research Center, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. yamashita@molneu.med.osaka-u.ac.jp.
10
Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. yamashita@molneu.med.osaka-u.ac.jp.

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.

PMID:
29311561
PMCID:
PMC5758562
DOI:
10.1038/s41598-017-18362-2
[Indexed for MEDLINE]
Free PMC Article

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