| Project/Area Number |
16K09728
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Nara Medical University |
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Principal Investigator |
Sugie Kazuma 奈良県立医科大学, 医学部, 教授 (60347549)
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| Co-Investigator(Kenkyū-buntansha) |
西野 一三 国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第一部, 部長 (00332388)
上野 聡 奈良県立医科大学, 医学部, 教授 (40184949)
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| Research Collaborator |
Ueno Satoshi
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 自己貪食空胞性ミオパチー / オートファジー / 自己貪食空胞 / ダノン病 / ミオパチー / 封入体筋炎 / Danon病 / 神経科学 / 脳神経疾患 / 臨床 / 病理学 |
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| Outline of Final Research Achievements |
In many muscle diseases, pathomechanism associated with autophagy system has not been well established. First, inclusion body myositis (IBM) may be caused by secondary dysfunction of autophagy. We identified muscle fibers with positive antibodies against cytosolic-5'-nucleotidase 1A pathologically in IBM. We considered that these expression leaded to high sensitivity and high specificity on the diagnosis of IBM. Next, Danon disease, an X-linked dominant vacuolar cardiomyopathy and skeletal myopathy, is caused by primary dysfunction of autophagy. On a nationwide survey in Japan, we identified 39 patients from 20 families with Danon disease. Cardiomyopathy, the main cause of death, was documented in all patients. In addition, we identified 12 patients from 4 families with XMEA. Pathologically, we found autophagic vacuoles with sarcolemmal features (AVSF) in both Danon disease and XMEA. AVSF expressed virtually all sarcolemmal proteins on their vacuolar membranes.
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| Academic Significance and Societal Importance of the Research Achievements |
オートファジー異常を原因とする希少難治性筋疾患において、疾患概念の確立や診断基準の整合性、治療法を含めた臨床病態について明らかにしてきた。このことは、本疾患患者の療養環境の改善に大きく貢献していると考える。また、病理学的なライソゾーム／オートファジー経路の病態への関与を明らかにしたことで、普遍的なオートファジーの解明、ひいてはオートファジー機構の分子病態解明から治療法の開発へつながり、社会的貢献は大きいと考える。
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