Drug development for intractable epilepsy based on ketogenic diet-derived metabolites
| Project/Area Number |
18H02719
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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| Research Institution | Okayama University |
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Principal Investigator |
Inoue Tsuyoshi 岡山大学, 医歯薬学総合研究科, 准教授 (40370134)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | ケトン食 / 治療薬開発 / 難治性てんかん / 乳酸脱水素酵素 / 電位依存性カルシウムチャネル / βヒドロキシ酪酸 / アルツハイマー病 / ケトン体 / 脳神経疾患 / 電気生理学 / 代謝物質 / てんかん / アセチルコリン |
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| Outline of Final Research Achievements |
The ketogenic diet treatment is effective for drug-resistant intractable epilepsy, and also potentially effective for other neurological disorders such as Alzheimer diseases. We addressed the following three issues in this study, towards the drug development based on the ketogenic diet. First, we focused on β-hydroxybutyrate, a main metabolite of the ketogenic diet, and determined the α1 subunit of voltage-dependent calcium channels that is inhibited by β-hydroxybutyrate. Second, we found that seizures in mice increase the LDHA subunit in the brain, which is a constituent of LDH enzymes that are responsible for the antiepileptic effects of the ketogenic diet. Finally, we found that β-hydroxybutyrate protects cognitive dysfunction in a mouse model of Alzheimer diseases, and investigated the protection mechanism.
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| Academic Significance and Societal Importance of the Research Achievements |
既存の治療薬が効かない「難治性神経疾患」の患者は、新しい作用機序を持つ新薬開発を必要としている。ケトン食療法は、難治性てんかんを代表とする神経疾患に有効であるが、厳しい食事制限ゆえに継続するのが難しく、「ケトン食療法に基づく治療薬」が望まれている。そこで本研究では、ケトン食によって産生される代謝産物を中心に、治療薬開発に必要な創薬標的分子の同定・検証実験を進め、３つの研究成果を得ることができた。
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Report
(4 results)
Research Products
(4 results)
