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Development of Nucleic Acid Therapeutics Using Microbubbles Combined with Ultrasound for Neurodegenerative Diseases.

Research Project

Project/Area Number 21K06846
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionTeikyo University

Principal Investigator

Kinoshita Chisato  帝京大学, 医学部, 講師 (10567085)

Co-Investigator(Kenkyū-buntansha) 青山 晃治  帝京大学, 医学部, 教授 (00420943)
鈴木 亮  帝京大学, 薬学部, 教授 (90384784)
松村 暢子  帝京大学, 医学部, 講師 (30317698)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords神経保護効果 / 核酸薬 / ドラッグデリバリー / 経鼻投与 / 神経変性疾患 / 内因性抗酸化物質 / 酸化ストレス / マイクロバブル / 脳内送達 / microRNA / 神経保護 / グルタチオン / マイクロバブル超音波法
Outline of Research at the Start

本研究の目的は、神経保護作用を呈する核酸薬を効率よく簡便に脳内に送達させる画期的な投与法としてマイクロバブル超音波法を用いた経鼻投与により、未だ根治療法が存在しない神経変性疾患の治療に効果的であるかを明らかにすることが目的である。マウスにおける神経変性疾患モデルにおいてマイクロバブル超音波法を用いた核酸薬経鼻投与が神経変性進行抑制、認知機能低下に対して有効かを立証するまでを本研究の課題とする。

Outline of Final Research Achievements

In previous research, I found that one of the microRNAs regulating the modulators of the endogenous antioxidant glutathione is important for antioxidant defense mechanisms against oxidative stress, a common etiological factor in neurodegenerative diseases.The administration of a nucleic acid drug regulating microRNA function resulted in neuroprotective effects.The purpose of this study is to establish a novel administration method using microbubbles combined with ultrasound for noninvasive intranasal delivery of nucleic acid drugs, aiming for clinical applications, and to determine its effectiveness in treating neurodegenerative diseases for which no curative therapy currently exists. The results show that therapy using microbubbles combined with ultrasound has been suggested to be effective in inhibiting neurodegeneration progression and mitigating cognitive decline in mouse models of neurodegenerative diseases.

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患では共通して酸化ストレスの亢進が病因や疾患進行に関与しているため、抗酸化物質グルタチオン合成の促進は疾患の予防及び治療に大きく寄与する。本研究では、核酸薬が効率的にグルタチオン合成を促進し、神経保護効果を有することで不治とされる神経変性疾患治療薬開発の礎になる。また、神経変性疾患は増悪の過程において、神経細胞の変性、脱落が起こるため、死に至るまでQOLが低下し続ける。治療薬開発によりの疾患進行を阻止出来れば個人的負担のみならず、社会的負担も大きく軽減することが可能となる。さらに神経変性疾患を予防することが出来れば、労働力として確保することも可能となることが期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (7 results)

All 2023 2022

All Presentation (6 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Presentation] Targeted Delivery of MicroRNA-96-5p Inhibitor in the Mouse Brain Using Microbubbles and Ultrasound Technology Enhances Neuroprotection via Increasing Glutathione Levels2023

    • Author(s)
      Chisato Kinoshita, Kazue Kikuchi-Utsumi, Koji Aoyama, Ryo Suzuki, Yayoi Okamoto, Nobuko Matsumura, Daiki Omata, Kazuo Maruyama, Toshio Nakaki
    • Organizer
      RNA Therapeutics: From Concept to Clinic
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TheNeuroprotective Effect of a miR-96-5p Inhibitor: Delivery to Brain via the Blood Brain Barrier2023

    • Author(s)
      Chisato Kinoshita, Koji Aoyama, Toshio Nakaki
    • Organizer
      8th Neurological Disorder Summit
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Inhibition of miR-96-5p in the mouse brain increases glutathione levels by indirectly modifying GTRAP3-18 expression.2023

    • Author(s)
      Chisato Kinoshita, Koji Aoyama, Ryo Suzuki, Nobuko Matsumura, Daiki Omata, Kazuo Maruyama, Toshio Nakaki
    • Organizer
      The 97th Annual Meeting of the Japanese Pharmacological Society
    • Related Report
      2023 Annual Research Report
  • [Presentation] マイクロバブル超音波技術を用いたmiR-96-5p機能抑制薬の脳内送達による神経保護作用とオートファジー活性化2022

    • Author(s)
      木下 千智
    • Organizer
      第96回 日本薬理学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] The neuroprotective effect of a miR-96-5p inhibitor delivery to brain using microbubbles and ultrasound technology.2022

    • Author(s)
      Chisato Kinoshita
    • Organizer
      14th International Conference on Dementia, Alzheimer and Related Diseases
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] マイクロバブル超音波技術を用いたmiR-96-5p阻害薬の脳内送達による神経保護効果およびミクログリア活性への影響2022

    • Author(s)
      木下 千智
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] MIR-96-5P INHIBITOR AND PHARMACEUTICAL COMPOSITION CONTAINING SAME2023

    • Inventor(s)
      Chisato Kinoshita
    • Industrial Property Rights Holder
      Chisato Kinoshita
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Acquisition Date
      2023
    • Related Report
      2023 Annual Research Report
    • Overseas

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Published: 2021-04-28   Modified: 2025-01-30  

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