Deciphering the mechanism of neuropathy and development of novel therapies in familial amyloid polyneuropathy
Project/Area Number |
17K09777
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Nagoya University |
Principal Investigator |
Koike Haruki 名古屋大学, 医学系研究科, 准教授 (80378174)
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Co-Investigator(Kenkyū-buntansha) |
飯島 正博 名古屋大学, 医学部附属病院, 特任准教授 (40437041)
川頭 祐一 名古屋大学, 医学部附属病院, 病院講師 (40569779)
勝野 雅央 名古屋大学, 医学系研究科, 教授 (50402566)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 家族性アミロイドポリニューロパチー / アミロイド / アミロイドーシス / トランスサイレチン / ニューロパチー / 家族性アミロイトポリニューロパチー |
Outline of Final Research Achievements |
Transthyretin (TTR) Val30Met familial amyloid polyneuropathy (FAP) (FAP ATTR Val30Met) is the most common type of FAP. Long amyloid fibers were abundant in the conventional early-onset Val30Met cases from endemic foci, whereas the amyloid fibrils were generally short in the late-onset Val30Met and non-Val30Met cases from non-endemic areas. The distortion of Schwann cells close to amyloid fibril masses was conspicuous, particularly in cases with long amyloid fibrils. Findings suggestive of the disruption of blood-nerve barriers, such as the loss of tight junctions and the fenestration of endothelial cells, were frequently found particularly in late-onset FAP cases. These findings suggest that direct insult of amyloid fibrils causes Schwann cell damage resulting in the predominant loss of small-fiber axons characteristic of early onset cases. In addition, vasculopathy may also participate in the pathogenesis of neuropathy, particularly in late onset cases.
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Academic Significance and Societal Importance of the Research Achievements |
遺伝子診断の進歩とともに家族性アミロイドポリニューロパチー(FAP)、特に高齢発症例は従来考えられていたよりも世界的に広範囲に存在すると考えられるようになっており、特に診断に難渋することの多い非集積地の高齢発症例に対する新規治療法の開発の重要性が高まっている。本研究の成果は、世界に先駆けてFAPの病態を従来型の集積地例における若年発症例と非集積地の高齢発症例を比較することによって明らかにするものであり、世界的にも注目されている。本研究によって明らかにされた病態、特に微小血管障害とアミロイド前駆体の毒性を抑制する治療戦略はFAP以外の疾患に対する新たな治療の確立にもつなげることが可能である。
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Report
(4 results)
Research Products
(37 results)
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[Journal Article] Common clinicopathological features in late-onset hereditary transthyretin amyloidosis (Ala97Gly, Val94Gly, and Val30Met).2019
Author(s)
Koike H, Nakamura T, Nishi R, Ikeda S, Kawagashira Y, Iijima M, Yasuda T, Mukai E, Date Y, Shiomi K, Nakazato M, Katsuno M, Sobue G.
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Journal Title
Related Report
Peer Reviewed
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[Presentation] Common clinicopathological features in late-onset hereditary ATTR amyloidosis (Ala97Gly, Val94Gly, and Val30Met).2018
Author(s)
Koike H, Nishi R, Ikeda S, Kawagashira Y, Iijima M, Yasuda T, Mukai E, Date Y, Shiomi K, Nakazato M, Katsuno.M, Sobue G
Organizer
The XVIth International Symposium on Amyloidosis
Related Report
Int'l Joint Research
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[Presentation] Patisiran, an investigational RNAi therapeutic for patients with hereditary transthyretin-mediated (hATTR) amyloidosis: Phase 3 APOLLO study subanalysis of Japanese patients.2018
Author(s)
Yamashita Y, Sekijima Y, Koike H, Ueda M, Yoshinaga T, Kodaira M, Sobue G, Katsuno M, Singh T, Hashimoto Y, Kadam K, Hou A, Ando Y
Organizer
The XVIth International Symposium on Amyloidosis
Related Report
Int'l Joint Research
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[Presentation] Common clinicopathological features in late-onset hereditary ATTR amyloidosis (Ala97Gly, Val94Gly, and Val30Met)2018
Author(s)
Koike H, Nishi R, Ikeda S, Kawagashira Y, Iijima M, Yasuda T, Mukai E, Date Y, Shiomi K, Nakazato M, Katsuno M, Sobue G
Organizer
The XVIth International Symposium on Amyloidosis
Related Report
Int'l Joint Research
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