Study for Pathogenesis of Cerebral Creatine Deficiency Syndromes
| Project/Area Number |
26461544
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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 |
Pediatrics
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| Research Institution | Kyoto University |
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Principal Investigator |
WADA Takahito 京都大学, 医学研究科, 准教授 (70359727)
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| Co-Investigator(Kenkyū-buntansha) |
立川 正憲 東北大学, 薬学研究科, 准教授 (00401810)
伊藤 慎悟 熊本大学, 大学院生命科学研究部(薬), 助教 (20466535)
新保 裕子 地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 研究員 (50724663)
小坂 仁 自治医科大学, 医学部, 教授 (90426320)
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| Research Collaborator |
OHTSUKI Sumio 熊本大学, 大学院生命科学研究部, 教授 (60323036)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 知的障害 / クレアチン / トランスポーター / 先天性代謝異常 / 脳クレアチン欠乏症候群 / 治療薬 / クレアチントランスポーター / 発達障害 / iPS細胞 / グアニジノ化合物 / クレアチニン / グアニジノ酢酸 / 精神遅滞 / 自閉症 |
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| Outline of Final Research Achievements |
Creatine transporter deficiency is caused by mutations of SLC6A8 gene, leading to low concentration of creatine in cells in the brain, and is characterized with intellectual disability, epilepsy, autistic spectrum disorders, and delayed speech development. The aim of this study is to clarify the pathogenesis of this disease. During this year, we have 1) established the system to register patients to collect their clinical and genetic information, 2) prepared patients-derived fibroblast and iPS cells as bioresources for basic research, 3) developed the system analyzing creatine matabolites by high-performance liquid chromatography, and 4) demonstrated that mutated transporter of a patient-derived cell localized abnormally in the cell, causing to reduce its transport ability. Our result suggests that the strategy to find a treatment for the patient is to search chemicals with ability to transfer the abnormally localized transporters to plasma membrane.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Urine screening for patients with developmental disabilities detected a patient with creatine transporter deficiency due to a novel missense mutation in SLC6A8.2014
Author(s)
Kato H, Miyake F, Shimbo H, Ohya M, Sugawara H, Aida N, Anzai R, Takagi M, Okuda M, Takano K, Wada T*, Iai M, Yamashita S, Osaka H.
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Journal Title
Brain Dev.
Volume: 36
Issue: 7
Pages: 630-633
DOI
Related Report
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[Presentation] Molecular genetic study and urine analysis of Japanese patients with cerebral creatine deficiency syndromes.2015
Author(s)
H. Shimbo, H. Osaka, M. Tachikawa, S. Ohtsuki, S. Ito, T. Goto, Y. Tsuyusaki, N. Aida, K. Kurosawa, Y. Kurosawa, H. Kato, K. Takano, T. Wada.
Organizer
65th American Society of Human Genetics
Place of Presentation
Baltimore
Year and Date
2015-10-06
Related Report
Int'l Joint Research
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[Presentation] Tatsuki Uemura, Shingo Ito, Yusuke Ota, Masanori Tachikawa, Takahito Wada, Mio Hirayama, Tetsuya Terasaki, Sumio Ohtsuki: Changes in transport activity and cellular localization by a novel missense mutation in human creatine transporter found in Japanese cerebral creatine deficiency syndromes patients2015
Author(s)
Tatsuki Uemura, Shingo Ito, Yusuke Ota, Masanori Tachikawa, Takahito Wada, Mio Hirayama, Tetsuya Terasaki, Sumio Ohtsuki
Organizer
Barcelona BioMed Conference Blood Braine Barrier
Place of Presentation
Barcelona, Spain
Year and Date
2015-10-02
Related Report
Int'l Joint Research
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