A Study on the Pathogenesis and Therapy of Optic-Spinal Multiple Sclerosis
| Project/Area Number |
17390250
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
ITOYAMA Yasuto TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院医学系研究科, 教授 (30136428)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIHARA Kazuo GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 大学院医学系研究科, 助教授 (70280873)
NAKASHIMA Ichiro HOSPITAL, ASSOCIATE RESEARCH, 病院・助手 (50333810)
KATO Hidemasa Biomedical Engineering Research Organazation, Associate Professor, 先進医工学研究機構, 助教授 (50292123)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2005: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | Multiple Sclerosis / Demyelinating disease / Optic-spinal MS / Conventional MS / Neuromyelitis optica / Anti-aquaporin-4 antibody |
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| Research Abstract |
In Japan, multiple sclerosis (MS) has been classified into two subtypes, 1) conventional MS (CMS) in which demyelinating lesions are disseminated in the central nervous system and 2) optic-spinal MS (OSMS) characterized by the selective involvement of the optic nerves and spinal cord. OSMS and Neuromyelitis optica (NMO) have many features in common. We investigated the pathogeneses and therapy of OSMS :
1. Features of NMO-IgG-positive cases
In 2004, we reported an NMO-OSMS-specific autoantibody, NMO-IgG. Longitudinally extensive. spinal cord lesions and blindness are commonly seen in NMO-IgG-positive patients. Also, some of them have unique brain lesions, such as longitudinally extensive lesions and periaqueductal lesions.
2. Establishment of a sensitive assay of anti-aquaporin-4 (AQP4) antibody
The target antigen of NMO-IgG was identified as AQP4 in 2005. We established a sensitive assay of anti-AQP4 antibody and found that about 90% of patients with NMO and the high-risk syndrome were seropositive, but none of the patients with MS and other diseases were positive for this autoantibody, suggesting that NMO is associated with anti-AQP4 antibody.
3. Loss of AQP4 in NMO lesions
We did a comparative neuropathological study of the spinal cord lesions of NMO and CMS. As a result, we found that in NMO AQP4 was completely lost in the perivascular regions where immunoglobulins and activated complements were deposited. The immunoreactivity of myelin basic protein was rather preserved. In contrast, AQP4 was upregulated in the demyelinating lesions of MS. These findings suggest that AQP4 densely expressed on the foot processes of astrocytes are targeted in NMO and that NMO is a distinct clinical entity from MS.
4. Therapy of NMO
We found that half of NMO patients who were refractory to high-dose IV methylprednisolone did respond to plasma exchange. We also found that long-term low-dose corticosteroid was effective to reduce relapses in NMO
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Report
(3 results)
Research Products
(117 results)
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[Journal Article] Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO : a study on antibody titer.2007
Author(s)
Takahashi T, Fujihara K, Nakashima 1, Misu T, Miyazawa I, Nakamura M, Watanabe S, Shiga Y, Kanaoka C, Fujimori J, Sato S, Itoyama Y.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Optic-Spinal Multiple Sclerosis.2006
Author(s)
Fujihara K, Nakashima I, Misu T, Miyazawa 1, Fujimori J, Narikawa K, Nakamura M, Takahashi T, Watanabe S, Sato S, Itoyama Y.
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Journal Title
Advances in Neurological Sciences 50
Pages: 549-557
Description
「研究成果報告書概要(欧文)」より
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[Book] Current Topics in Neuroimmunology (1^<st>edition) (ed by Tabira T, Yamamura T, Kira J.)2006
Author(s)
Fujihra K, Nakashima I, Misu T, Takahashi T, Watanabe S, Nakamura M, Miyazawa I, Fujimori J, Narikawa K, Sato S, Itoyama Y
Publisher
Medimond, Bologna
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Book] Quick Reference Guide for Managementoin Orthopaedies(139edifion)2006
Author(s)
Fujihara K.Multiple Sclerosis.Ed by Moriya H, Homan M, Uchida A, Hagino T, Kurosaka M, Toyama Fujihara K.Multiple Sclerosis.Ed by Moriya H, Homan M, Uchida A, Hagino T, Kurosaka M, Toyama Y
Publisher
Bunkodo, Tokyo
Description
「研究成果報告書概要(欧文)」より
Related Report
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