• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The gene therapy for hypophosphatasia animal model

Research Project

Project/Area Number 15K09605
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNippon Medical School

Principal Investigator

Matsumoto Tae  日本医科大学, 医学部, 助教 (10366742)

Co-Investigator(Kenkyū-buntansha) 三宅 弘一  日本医科大学, 医学部, 准教授 (90267211)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords低ホスファターゼ血症 / アルカリホスファターゼ / 遺伝子治療 / AAVベクター / AAVベクター / ALP / 低ホスファターゼ症 / ALP
Outline of Final Research Achievements

Hypophosphatasia is an inherited skeletal disease characterized by defective bone and teeth mineralization due to the deficiency of tissue-nonspecific alkaline phosphatase (TNALP), which leads to abnormal mineralization of skeletal and dental tissues. TNALP knockout (Akp2-/-) mice are good models for infantile HPP.We used a single intramuscular injection of Adeno associated vector type 8 (AAV8)with a bone-targeted form of human TNALP in which a deca-aspartate sequence is linked to the C terminal end of soluble TNALP (TNALP-D10) to prolong Akp2-/- mice life with insufficient bone maturity.Treated Akp2-/- mice with AAV8-TNALP-D10 lived longer than 1 year with normal physical activity and healthy appearance, while control Akp2-/- mice died in 3 weeks. At 18 months, bone mineral density and bone volume/tissue volume values were close to those of control ones. The success of intramuscular gene therapy for Akp2-/- mice with AAV8-TNALP-D10 shows possibility to achieve human therapy.

Academic Significance and Societal Importance of the Research Achievements

低ホスファターゼ血症はヒトでは多様な重症度を示し、重症型では骨形成が不十分で胸郭の形態が維持されず呼吸不全で出生後早期に死亡することもあるが、軽症でも乳歯脱落のため義歯が必要であったり骨折をおこしやすく、生活の質がさがりやすい。単一遺伝子の異常によりおこるアルカリホスファターゼ酵素欠損による疾患であり、遺伝子治療で、体内でアルカリホスファターゼ産生ができるようになれば治療意義が大きい。
AAV8-TNALP-D10 ベクターの筋肉注射での治療成功は、ただ一回のベクター局所投与でのヒトでの治療可能性を示した、臨床応用に大きな一歩と言える。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (3 results)

All 2018

All Presentation (2 results) Book (1 results)

  • [Presentation] Direct comparison between single-stranded and self-complementary type 9 AAV vector to treat adult MLD model mice by intravenous injection.2018

    • Author(s)
      Noriko Miyake, Koichi Miyake, Motoko Yamamoto, Takashi Shimada, Takashi Okada.
    • Organizer
      The 24th Annual Meeting of Japan Society of Gene Therapy
    • Related Report
      2018 Annual Research Report
  • [Presentation] Intravitreal injection of AAV vector in cynomolgus monkeys affects neutralizing antibody titer against AAV in the serum.2018

    • Author(s)
      Tsutomu Igarashi, Kazuhisa Takahashi, Koichi Miyake, Maika Kobayashi, Chiemi Yaguchi, Noriko Miyake, Shuhei Kameya, Hiroshi Takahashi, Takashi Okada
    • Organizer
      The 24th Annual Meeting of Japan Society of Gene Therapy
    • Related Report
      2018 Annual Research Report
  • [Book] Neonatal Gene Therapy for Inherited Disorders. Selected Topics in Neonatal Care.2018

    • Author(s)
      Miyake K, Miyake N, Shimada T.
    • Total Pages
      9
    • Publisher
      InTech
    • Related Report
      2018 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi