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

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K08262
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Jikei 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
• Keywords: ムコ多糖症II型 / 遺伝子治療

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.

Free Research Field

遺伝子治療

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。