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Hematopoietic stem cell gene therapy using engineered enzyme with high penetrating ability for mucopolysaccharidosis type II

Research Project

Project/Area Number 19K08262
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionJikei University School of Medicine

Principal Investigator

SHIMADA Yohta  東京慈恵会医科大学, 医学部, 講師 (20560824)

Co-Investigator(Kenkyū-buntansha) 樋口 孝  東京慈恵会医科大学, 医学部, 講師 (30595327)
大橋 十也  東京慈恵会医科大学, 医学部, 教授 (60160595)
小林 博司  東京慈恵会医科大学, 医学部, 教授 (90266619)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsムコ多糖症II型 / 遺伝子治療 / ライソゾーム病
Outline of Research at the Start

ムコ多糖症II型(MPS II)はイズロン酸-2-スルファターゼ(IDS)という酵素が生まれつき足りないために生じる病気であり、発達の遅れや骨格の変形など全身に様々な症状が現れる。現在のところMPS IIの全ての症状を治癒する有効な治療法は存在せず、新たな治療法の開発が望まれている。本研究では、MPS IIに有効な遺伝子治療法の開発を目的に、通常のIDSよりも細胞に取り込まれ易いように改変したIDSを組み込んだウイルスベクターを作成し、同ベクターによる造血幹細胞を標的とした遺伝子治療の有効性についてMPS IIモデルマウスを用いて評価する。

Outline of Final Research Achievements

Mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal storage disease caused by a deficiency of iduronate-2- sulfatase (IDS). Progressive accumulation of glycosaminoglycan (GAG), which is the substrate of IDS, leads to various symptoms including central nervous system involvement. In this study, we analyzed the efficacy of hematopoietic stem cell gene therapy (HSCGT) using engineered IDS with high penetrating ability on a murine model of MPS II. Similar GAG reduction was observed in the visceral organs of MPS II mice between HSGCT using engineered IDS and control IDS. However, HSCGT using engineered IDS improved the GAG accumulation in CNS of MPS II mice compared to HSCGT using control IDS.

Academic Significance and Societal Importance of the Research Achievements

現在、MPS IIに対する治療としては酵素補充療法や造血幹細胞移植が存在するが、一度の治療介入で中枢神経を含む全身の病変の根治が期待できる治療法は存在しない。本研究の成果は、細胞への移行能を向上させたIDSを用いた造血幹細胞遺伝子治療が一度の治療介入で中枢神経を含む各種臓器に高い有効性をもたらすことをモデルマウスで初めて明らかにするものであり、学術的意義は高い。また、本成果は将来的な臨床応用にもつながる成果であり、社会的意義も大きいと言える。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (5 results)

All 2023 2022 2021

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] A novel preclinical model of mucopolysaccharidosis type II for developing human hematopoietic stem cell gene therapy2023

    • Author(s)
      Shimada Y, Ishii N, Higuchi T, Goto M, Ohashi T, Kobayashi H
    • Journal Title

      Gene Therapy

      Volume: 30 Issue: 3-4 Pages: 288-296

    • DOI

      10.1038/s41434-022-00357-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Presentation] Application of a novel murine model of mucopolysaccharidosis type II for developing human hematopoietic stem cell gene therapy2022

    • Author(s)
      Shimada Y, Ishii N, Higuchi T, Goto M, Ohashi T, Kobayashi H
    • Organizer
      25th Annual Meeting of The American Society of Gene and Cell Therapy
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Hematopoietic stem cell gene therapy for mucopolysaccharidosis type II2021

    • Author(s)
      Shimada Y
    • Organizer
      The 27th annual meeting of Japan Society of Gene and Cell Therapy
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Analysis of human hematopoietic stem cell gene therapy using mucopolysaccharidosis type II mice2021

    • Author(s)
      Shimada Y, Ishii N, Higuchi T, Ohashi T, Kobayashi H
    • Organizer
      第62回日本先天代謝異常学会
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 中枢神経系疾患の治療のための、核酸分子、ベクター、組換え細胞及び薬剤2022

    • Inventor(s)
      木下正文、高木春奈、薗田啓之、嶋田洋太、小林博司、他
    • Industrial Property Rights Holder
      JCRファーマ株式会社
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-110492
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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