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Multiple development of treatment for pulmonary arterial hypertension by constitutive active natriuretic peptide receptor

Research Project

Project/Area Number 15K09690
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionOsaka University

Principal Investigator

Kogaki Shigetoyo  大阪大学, 医学系研究科, 招へい教員 (00311754)

Co-Investigator(Kenkyū-buntansha) 高橋 邦彦  大阪大学, 医学系研究科, 招へい教員 (10610230)
那波 伸敏  大阪大学, 医学部附属病院, 医員 (30617543)
馬殿 洋樹  大阪大学, 医学部附属病院, 医員 (60644614)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords小児循環器学 / 肺高血圧症 / 遺伝子治療
Outline of Final Research Achievements

We analyzed the effect of the induction of constitutive active NPR2, which could produce massive cGMP compared to other drugs. NPR2 was induced by using Sendai-virus vectors into Sugen-Hypoxia model rat which was shown as very similar to human pulmonary hypertension. First we confirmed the safety of this treatment by immunostaining of Sendai virus, which showed no infection except for lungs. The NPR2 induction leaded significant improvement of pulmonary arterial pressure by catheter examination. In histologically, NPR2 induction demonstrated the improvement of medial wall thickness of pulmonary resistant arteries as well as the supression of small pulmonary vessel occlusion.
Next, we identified candidate small compounds, which allowed to access and stimulate guanylyl cyclase activity of NPR2 by using in silico modeling of the molecular structure of NPR2. However no small compound showed significant superior stimulative activity compared to existing drugs.

Report

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

    (7 results)

All 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension.2016

    • Author(s)
      Nawa N, Ishida H, Katsuragi S, Baden H, Takahashi K, Higeno R, Torigoe F, Mihara S, Narita J, Miura K, Nakamura K, Kogaki S, Ozono K.
    • Journal Title

      Mol Ther Methods Clin Dev

      Volume: 3 Pages: 16044-16044

    • DOI

      10.1038/mtm.2016.44

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic predictive value of gene mutations in Japanese patients with hypertrophic cardiomyopathy.2016

    • Author(s)
      Chida A, Inai K, Sato H, Shimada E, Nishizawa T, Shimada M, Furutani M, Furutani Y, Kawamura Y, Sugimoto M, Ishihara J, Fujiwara M, Soga T, Kawana M, Fuji S, Tateno S, Kuraishi K, Kogaki S, Nishimura M, Ayusawa M, Ichida F, Yamazawa H, Matsuoka R, Nonoyama S, Nakanishi T.
    • Journal Title

      Heart Vessels

      Volume: Nov 24 Issue: 6 Pages: 700-707

    • DOI

      10.1007/s00380-016-0920-0

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] B型ナトリウム利尿ペプチド受容体(NPR-B)機能獲得変異体による心不全予防効果の検討2016

    • Author(s)
      馬殿洋樹,桂木慎一,那波伸敏,石田秀和,成田淳,高橋邦彦,小垣滋豊,大薗恵一
    • Organizer
      第52回日本小児循環器学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Intravascular injection of Sendai virus vector carrying continuously cGMP producing mutant of type B Natriuretic Peptide Receptor can ameliorate pulmonary arterial hypertension.2015

    • Author(s)
      Nawa N, Ishida H, Katsuragi S, Baden H, Takahashi K, Kogaki S, Higeno R, Torigoe F, Mihara S, Narita J, Miura K, Ozono K
    • Organizer
      American Heart Association (AHA) Scientific Sessions 2015
    • Place of Presentation
      Orlando, Florida, United States
    • Year and Date
      2015-11-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] CNP受容体恒常活性型変異体を用いた肺高血圧症の新たな治療法2015

    • Author(s)
      那波 伸敏、石田 秀和、馬殿 洋樹、桂木 慎一、高橋 邦彦、小垣 滋豊、廣瀬 将樹、鳥越 史子、髭野 亮太、三原 聖子、成田 淳、三浦 弘司、大薗 恵一
    • Organizer
      第4回日本肺循環学会・第3回日本肺高血圧学会 合同学術集会
    • Place of Presentation
      ステーションコンファレンス東京
    • Year and Date
      2015-10-03
    • Related Report
      2015 Research-status Report
  • [Presentation] センダイウイルスベクターを用いた 肺動脈性肺高血圧症(PAH)に対する新たな遺伝子治療の可能性2015

    • Author(s)
      那波 伸敏、石田 秀和、馬殿 洋樹、高橋 邦彦、小垣 滋豊、廣瀬 将樹、桂木 慎一、髭野 亮太、三原 聖子、成田 淳、三浦 弘司、大薗 恵一
    • Organizer
      第51回日本小児循環器学会総会・学術集会
    • Place of Presentation
      ホテル日航東京
    • Year and Date
      2015-07-16
    • Related Report
      2015 Research-status Report
  • [Presentation] Therapeutic application of constitutively active type B natriuretic peptide receptor for pulmonary arterial hypertension2015

    • Author(s)
      Nawa N, Ishida H, Baden H, Takahashi K, Higeno R, Mihara S, Ishii R, Ichimori H, Yabushita-Okada Y, Miura K, Kogaki S, Ozono K
    • Organizer
      第79回日本循環器学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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