Experimental study in new drugs for stroke and Amyotrophic lateral sclerosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08317
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Nihon University
• Principal Investigator: ISHIGE Kumiko 日本大学, 薬学部, 教授 (40212873)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: GR103691 / 脳梗塞 / 酸化ストレス / 細胞死

Outline of Final Research Achievements

The present study aims to establish the new candidate for therapeutic drugs in stroke and amyotrophic lateral sclerosis (ALS).In the HT22 cells, derived from a mouse hippocampal neuron, it was demonstrated that edaravone, GR and GR related compounds suppressed glutamic acid (Glu)-induced cell death by oxidative stress. Western blot revealed that nuclear Lamin B1 but not Histone H3 is decreased before the cell death. Edaravone and GR related compound suppressed the infarct volume as identified by TTC staining at 24 h after irradiation in the stroke model induced by rose bengal injection and irradiation of middle cerebral artery. In addition, both drugs also suppressed behavioral score (locomotor activities, vertical activities and neuropathy scores assessed by posture, tail suspension test and platform walk test). These results suggest that GR related compound is useful as a candidate for new therapeutic drug of the diseases caused by oxidative stress including stroke.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

ラジカルスカベンジャーであるエダラボンは脳梗塞の後遺症軽減および、ほとんど治療法のないALSにおける進行抑制に寄与すると考えられるが、無効症例や禁忌症例があり、また副作用のために使用できない場合もある。両疾患においてエダラボンの代わりとなる薬物も存在しない。脳梗塞の後遺症により要介護者となる人は、要介護者全体の約3割を占めると推定されており、後遺症軽減は、社会的にも非常に有意義である。また、ALSは、現在、根本治療法が存在しないため、進行抑制に関与する薬物の選択肢を増やすことは重要な課題である。これらよりGR関連化合物がエダラボンの代替え薬となる可能性を示した本研究の意義は大きい。