Drug development for intractable epilepsy by targeting lactate dehydrogenase

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07966
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Okayama University
• Principal Investigator: Inoue Tsuyoshi 岡山大学, 医歯薬学総合研究科, 准教授 (40370134)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 難治性てんかん / ケトン食療法 / 乳酸脱水素酵素 / スチリペントール / ケトン体 / 電位依存性カルシウムチャネル / 興奮性シナプス / アセチルコリン

Outline of Final Research Achievements

We addressed the following three issues in this study, in order to clarify the mechanisms that control "drug-resistant intractable epilepsy" and to develop new antiepileptic drugs based on the mechanisms. First, we focused on "ketogenic diet treatment" that is effective for the drug-resistant epilepsy, and identified a lactate dehydrogenase inhibitor that suppresses seizures in vivo. Second, we found that acetoacetate (a ketogenic diet-derived metabolite) inhibits voltage-dependent calcium channels, and then identified an acetoacetate analog that suppresses seizures in vivo. Finally, we found that acetylcholine is involved in the seizure control in a mouse model of drug-resistant epilepsy

Free Research Field

神経生理学