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Functional regeneration after ischemic stroke with mRNA therapy: Enhancement of cortical plasticity

Research Project

Project/Area Number 19K18381
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Fukushima Yuta  東京医科歯科大学, 生体材料工学研究所, 助教 (40837895)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords脳梗塞 / mRNA医薬 / 神経再生 / アストロサイト / リハビリテーション / 反応性アストロサイト / 運動機能代償野 / 神経機能再生
Outline of Research at the Start

脳梗塞後、定着した神経学的後遺症を改善する治療法は存在しない。本研究の概要は、脳梗塞モデル動物を用いて、脳梗塞発症早期リハビリテーションによる神経機能障害の改善をもたらす発現遺伝子を同定した上で、得られた遺伝子を、独自のmRNAデリバリー技術を用いて強制発現することで、定着した神経学的後遺症の機能改善を図ることである。mRNA医薬により、神経機能再生をもたらす新たな治療法開発を目的とした研究である。

Outline of Final Research Achievements

The animal model that mimics the difference between the early and late rehabilitation in human ischemic stroke patients well was established. It was elucidated that astrocytes were related to the obstruction of functional improvement with late rehabilitation in the model. These findings support the future application of mRNA therapeutics to functional regeneration therapy after ischemic stroke.

Academic Significance and Societal Importance of the Research Achievements

本研究は、長く待ち望まれる神経再生医療にmRNA医薬を応用することで革新的な治療法開発を目指す、その端緒を開くものである。mRNA医薬は、タンパク質を、生理的に、生体内で産生することが可能であるが、これは生体に潜在する能力を一時的に増強し、医療に応用できることを意味する。本研究で運動機能リハビリテーションの臨床像を反映する動物モデルを確立できたことは、神経再生医療を実現し社会に大きく還元するための礎を築いたものであると考える。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (10 results)

All 2021 2020 2019 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 3 results) Remarks (2 results)

  • [Journal Article] Treatment of ischemic neuronal death by introducing brain-derived neurotrophic factor mRNA using polyplex nanomicelle2021

    • Author(s)
      Y. Fukushima, S. Uchida, H. Imai, H. Nakatomi, K. Kataoka, N. Saito, K. Itaka
    • Journal Title

      Biomaterials

      Volume: 270 Pages: 120681-120681

    • DOI

      10.1016/j.biomaterials.2021.120681

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancement of motor function 1 recovery after spinal cord injury in mice by delivery of brain derived neurotrophic factor mRNA.2019

    • Author(s)
      S. T. Crowley, Y. Fukushima, S. Uchida, K. Kataoka, K. Itaka
    • Journal Title

      Mol. Ther. Nucleic Acids

      Volume: 17 Pages: 465-476

    • DOI

      10.1016/j.omtn.2019.06.016

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Intraventricular BDNF mRNA administration prevents ischemic neuronal death with the uptake predominantly by astrocytes2020

    • Author(s)
      Fukushima Y, Itaka K.
    • Organizer
      8th International mRNA Health Conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mRNA therapeutics for ischemic neuronal death: Intraventricular administration of BDNF mRNA using polyplex nanomicelles.2019

    • Author(s)
      Fukushima Y, Uchida S, Kataoka K, Itaka K.
    • Organizer
      19th Symposium for Gene Design and Delivery.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] mRNA医薬の脳神経保護薬への展開:BDNF mRNAのナノミセルによる脳室内投与2019

    • Author(s)
      福島 雄大,内田 智士,片岡 一則,位髙 啓史.
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] BDNF mRNA therapeutics for ischemic neuronal death.2019

    • Author(s)
      Fukushima Y, Uchida S, Kataoka K, Itaka K.
    • Organizer
      7th International mRNA Health Conference.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] mRNA医薬による虚血性中枢神経疾患神経保護治療2019

    • Author(s)
      福島 雄大,位髙 啓史.
    • Organizer
      第4回日本遺伝子細胞治療学会若手研究会セミナー
    • Related Report
      2019 Research-status Report
  • [Presentation] BDNF-expressing mRNA medicine for central nervous system disorders.2019

    • Author(s)
      Fukushima Y,Crowley TS,Itaka K.
    • Organizer
      第6回COINSシンポジウム
    • Related Report
      2019 Research-status Report
  • [Remarks] プレスリリース「メッセンジャーRNA医薬の新しい展開:脳虚血性疾患に対する新たな治療法開発」

    • URL

      https://www.tmd.ac.jp/press-release/20210128_1/

    • Related Report
      2020 Annual Research Report
  • [Remarks] A new agent for the brain diseases: mRNA

    • URL

      https://www.eurekalert.org/pub_releases/2021-04/tmad-ana040821.php

    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2022-01-27  

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