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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aquaporin 4 / genetics
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Aquaporin 4 / metabolism
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Astrocytes / metabolism
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Autoimmunity
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Disease Models, Animal
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GPI-Linked Proteins
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Gene Expression
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Glial Fibrillary Acidic Protein / genetics
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Glial Fibrillary Acidic Protein / metabolism
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Humans
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Immunoglobulin G / immunology*
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Immunoglobulin G / pharmacology
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / immunology*
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Nerve Tissue Proteins / antagonists & inhibitors
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Nerve Tissue Proteins / immunology*
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Neuromyelitis Optica / diagnosis
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Neuromyelitis Optica / drug therapy
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Neuromyelitis Optica / immunology*
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Neuromyelitis Optica / metabolism
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Neurons / immunology
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Neurons / metabolism
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Rats
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Severity of Illness Index
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Spinal Cord / immunology
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Spinal Cord / metabolism
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Spinal Cord / pathology
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Th17 Cells / immunology
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Th17 Cells / metabolism
Substances
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Aquaporin 4
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GFAP protein, rat
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GPI-Linked Proteins
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Glial Fibrillary Acidic Protein
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Immunoglobulin G
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Membrane Proteins
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Nerve Tissue Proteins
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RGMA protein, rat