A drug screening system for ALS by automated, quantitative motility analysis of C. elegans ALS model
Project/Area Number |
26670439
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Neurology
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Research Institution | Nagoya University |
Principal Investigator |
Sobue Gen 名古屋大学, 医学(系)研究科(研究院), 特任教授 (20148315)
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Co-Investigator(Kenkyū-buntansha) |
Katsuno Masahisa 名古屋大学, 大学院医学系研究科, 教授 (50402566)
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Co-Investigator(Renkei-kenkyūsha) |
Mori Ikue 名古屋大学, 大学院理学系研究科, 教授 (90219999)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 筋萎縮性側索硬化症 / 薬剤スクリーニング / 低分子化合物 / トランスレーショナルリサーチ / 線虫 |
Outline of Final Research Achievements |
There has not been reliable method for in vivo high-throughput quantification of the drug effects. Recently our collaborator developed a real-time computer vision system, the Multi worm tracker(WMT), that can quantify the behavior of dozens of worms. Using this system, we explored the effective drug for the ALS model animals, dnc-1KD worm, in which the dynactin 1 is knocked down in the motor neurons. This model shows the motor neuronal degeneration, and it mimics a several significant features of ALS pathology. We first chose rapamycin as a positive control and showed the effect in a dose dependent manner. Next, we screened the 50 drugs and identified two compounds which significantly rescued the motor deficit of the worm. Interestingly, one of the drug was Riluzole, which is one of the only two drugs approved for ALS in Japan. The other drug X is an anti-hypertensive drug. This method allow us to complete a drug screen in a few weeks compared with a few years when using rodent models.
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort2016
Author(s)
Ryoichi Nakamura, Jun Sone, Naoki Atsuta, Genki Tohnai, Hazuki Watanabe, Daichi Yokoi, Masahiro Nakatochi, Hirohisa Watanabe, Mizuki Ito, Jo Senda, Masahisa Katsuno, Fumiaki Tanaka, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe.
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Journal Title
Neurobiology of Aging
Volume: 39
Pages: 219-219
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Head Lift Exercise Improves Swallowing Dysfunction in Spinal and Bulbar Muscular Atrophy2015
Author(s)
Mano T, Katsuno M, Banno H, Suzuki K, Suga N, Hashizume A, Araki A, Hijikata Y, Tanaka S, Takatsu J, Watanabe H, Yamamoto M, Sobue G
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Journal Title
Eur Neurol
Volume: 74
Issue: 5-6
Pages: 251-258
DOI
Related Report
Peer Reviewed
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[Journal Article] Overexpression of hepatocyte growth factor in SBMA model mice has an additive effect on combination therapy with castration.2015
Author(s)
Ding Y, Adachi H, Katsuno M, Huang Z, Jiang YM, Kondo N, Iida M, Tohnai G, Nakatsuji H, Funakoshi H, Nakamura T, Sobue G
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Journal Title
Biochem Biophys Res Commun
Volume: 468
Issue: 4
Pages: 677-683
DOI
Related Report
Peer Reviewed
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[Journal Article] FUS regulates AMPA receptor function and FTLD/ALS-associated behaviour via GluA1 mRNA stabilization.2015
Author(s)
Udagawa, T., Fujioka, Y., Tanaka, M., Honda, D., Yokoi, S., Riku, Y., Ibi, D., Nagai, T., Yamada, K., Watanabe, H., Katsuno, M., Inada, T., Ohno, K., Sokabe, M., Okado, H., Ishigaki S*., and Sobue, G.
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Journal Title
Nat Commun
Volume: 6
Issue: 1
Pages: 7098-7098
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A functional scale for spinal and bulbar muscular atrophy: Cross-sectional and longitudinal study.2015
Author(s)
Hashizume A, Katsuno M, Suzuki K, Banno H, Suga N, Mano T, Araki A, Hijikata Y, Grunseich C, Kokkinis A, Hirakawa A, Watanabe H, Yamamoto M, Fischbeck KH, Sobue G
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Journal Title
Neuromuscul Disord.
Volume: 25
Issue: 7
Pages: 554-562
DOI
Related Report
Peer Reviewed
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[Journal Article] Pioglitazone suppresses neuronal and muscular degeneration caused by polyglutamine-expanded androgen receptors.2015
Author(s)
Iida M, Katsuno M, Nakatsuji H, Adachi H, Kondo N, Miyazaki Y, Tohnai G, Ikenaka K, Watanabe H, Yamamoto M, Kishida K, Sobue G
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Journal Title
Hum Mol Genet.
Volume: 24
Issue: 2
Pages: 314-329
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Factors affecting longitudinal functional decline and survival in amyotrophic lateral sclerosis patients.2014
Author(s)
Watanabe H, Atsuta N, Nakamura R, Hirakawa A, Watanabe H, Ito M, Senda J, Katsuno M, Izumi Y, Morita M, Tomiyama H, Taniguchi A, Aiba I, Abe K, Mizoguchi K, Oda M, Kano O, Okamoto K, Kuwabara S, Hasegawa K, Imai T, Aoki M, Tsuji S, Nakano I, Kaji R, Sobue G.
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Journal Title
Amyotroph Lateral Scler Frontotemporal Degener.
Volume: Epub ahead of print
Issue: 3-4
Pages: 230-6
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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