Development of effective evaluation method of bezafibrate for the fatty acid metabolism disorders using the iPS cells
Project/Area Number |
16K21179
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
Embryonic/Neonatal medicine
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Research Institution | Shimane University |
Principal Investigator |
Yamada Kenji 島根大学, 学術研究院医学・看護学系, 助教 (70624930)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | 脂肪酸代謝異常症 / ベザフィブラート / 代謝性ミオパチー / in vitro probe assay / 脂肪酸代謝能 / VLCAD欠損症 / CPT2欠損症 / FAOフラックス / 臨床治験 / in vitro prove assay / iPS細胞 / グルタル酸血症2型 / 酵素 / 脂肪酸代謝 |
Outline of Final Research Achievements |
Although bezafibrate has been reported as a hopeful drug for fatty acid oxidation disorders (FAOD) in in vitro, a clinical trial showed no obvious efficacy. However, the clinical symptom was clearly improved in some patients. Therefore, I thought that its efficacy could not be completely denied, and the measurement of fatty acid oxidation capacity might be inappropriate. In this study, I initially planned to develop and investigate a method for predicting the efficacy of bezafibrate using iPS cells. However, as a result, I found that modified conventional methods using fibroblasts derived from patients with FAOD, such as in vitro probe assay and fatty acid oxidation flux, can partially predict the efficacy of bezafibrate.
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Academic Significance and Societal Importance of the Research Achievements |
本研究結果はベザフィブラートの有効性を患者細胞を用いて予測するだけでなく、他の治療候補薬剤の有効性を検討することにも応用できる。本研究で発展させた脂肪酸代謝能の測定技術は一度に数~十数種類の薬剤を簡便に調べることが出来る。つまり、現時点ではベザフィブラートも含めて証明された治療薬のない脂肪酸代謝異常症への治療薬を探索する際に、患者由来の培養細胞を用いることで、安全に多数の薬剤を網羅的に検討できる。 さらに、脂肪酸代謝異常症だけでなく、ミトコンドリア病といった他の先天代謝異常症の治療薬の有効性を調べることにも応用できると思われる。
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Report
(5 results)
Research Products
(37 results)
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[Journal Article] Diagnostic potential of stored dried blood spots for inborn errors of metabolism: a metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency2018
Author(s)
Noriyuki Kaku, Kenji Ihara, Yuichiro Hirata, Kenji Yamada, Sooyoung Lee, Hikaru Kanemasa, Yoshitomo Motomura, Haruhisa Baba, Tamami Tanaka, Yasunari Sakai, Yoshihiko Maehara, Shouichi Ohga
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Journal Title
Journal of Clinical Pathology
Volume: 71
Issue: 10
Pages: 885-889
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Open-label clinical trial of bezafibrate treatment in patients with fatty acid oxidation disorders in Japan2018
Author(s)
Yamada K, Shiraishi H, Oki E, Ishige M, Fukao T, Hamada Y, Sakai N, Ochi F, Watanabe A, Kawakami S, Kuzume K, Watanabe K, Sameshima K, Nakamagoe K, Tamaoka A, Asahina N, Yokoshiki S, Miyakoshi T, Ono K, Oba K, Isoe T, Hayashi H, Yamaguchi S, Sato N
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Journal Title
Molecular Genetics and Metabolism Reports
Volume: 15
Pages: 55-63
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Newborn screening for carnitine palmitoyltransferase II deficiency using (C16 + C18:1)/C2: Evaluation of additional indices for adequate sensitivity and lower false-positivity2017
Author(s)
Tajima G, Hara K, Tsumura M, Kagawa R, Okada S, Sakura N, Maruyama S, Noguchi A, Awaya T, Ishige N, Musha I, Ajihara S, Ohtake A, Naito E, Hamada Y, Kono T, Asada T, Sasaio H, Fukaoo T, Fujikip R, Ohara O, Bo R, Yamada K, Kobayashi H, Hasegawa Y, Yamaguchi S, Takayanagis M, Hata I, Shigematsu Y, Kobayashi M
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Journal Title
Molecular Genetics and Metabolism
Volume: 122
Issue: 3
Pages: 67-75
DOI
Related Report
Peer Reviewed / Open Access
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