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Basic research of GDF15 therapy for mitochondrial diseases/metabolic syndrome

Research Project

Project/Area Number 18K07892
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 InstitutionKurume University

Principal Investigator

Koga Yasutoshi  久留米大学, 医学部, 教授 (00225400)

Co-Investigator(Kenkyū-buntansha) 八ツ賀 秀一  久留米大学, 医学部, 講師 (10454919)
喜多村 美幸  久留米大学, 医学部, 助教 (70772911)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsGDF15 / 診断薬 / 感度 / 特異度 / サイトカイン / ミトコンドリア病 / バイオマーカー / 電子伝達系酵素欠損 / 臨床性能試験 / サロゲートマーカー / ミトコンドリア機能不全 / 高乳酸血症 / 糖尿病 / インフルエンザ脳症 / 自己免疫性肝炎 / 原発性肝硬変 / 診断バイオマーカー / 病勢のバイオマーカー / 治療効果判定のバイオマーカー / メタボリック症候群 / メタボローム解析 / 治療薬開発
Outline of Final Research Achievements

We have identified GDF15, a new diagnostic biomarker for mitochondrial disease, and obtained the patent (P6711966). Under the collaborative study with Medical and Biological Laboratories Co., Ltd. (MBL), we developed a new diagnostic device (LTIA device) as an automated diagnostic indication test for MDs, and examined the equivalency of specificity and sensitivity in measuring serum GDF15 concentrations. The sensitivity and specificity of LTIA device showed 94% and 91%, respectively. The LTIA device of GDF15 may be a sufficiently reliable, frontline, diagnostic indicator of individuals with suspected MDs in the general population.

Academic Significance and Societal Importance of the Research Achievements

GDF15は、細胞が障害された場合に誘導されるTGFβ遺伝子ファミリーに属する生体内活性物質であり、その生物学的意義はいまだ不明である。今回、GDF15のミトコンドリア病に対する診断薬を開発したことで、未診断症例の早期発見や早期治療が可能となる。また、診断薬としての適応症取得や薬価収載になる事で、今まで解明されていない種々の病気、病態における研究が可能となり、GDF15の生物学的意義も解明されるものと期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Growth Differentiation Factor 15 as a useful biomarker of heart failure in young patients with unrepaired congenital heart disease of left to right shunt2020

    • Author(s)
      Kagiyama Y, Yatsuga S, Kinoshita M, Koteda Y, Kishimoto S, Koga Y, Suda K.
    • Journal Title

      J Cardiol.

      Volume: 75 Issue: 6 Pages: 697-701

    • DOI

      10.1016/j.jjcc.2019.12.008

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new diagnostic indication device of a biomarker growth differentiation factor 15 for mitochondrial diseases: From laboratory to automated inspection2020

    • Author(s)
      Koga Yasutoshi、Povalko Nataliya、Inoue Eisuke、Ishii Akiko、Fujii Katsunori、Fujii Tatsuya、Murayama Kei、Mogami Yukiko、Hata Ikue、Ikawa Masamichi、Fukami Kei、Fukumoto Yoshihiro、Nomura Masatoshi、Ichikawa Kazuki、Yoshida Kaori
    • Journal Title

      Journal of Inherited Metabolic Disease

      Volume: 44 Issue: 2 Pages: 358-366

    • DOI

      10.1002/jimd.12317

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial research in Asia: A step for the mito-global conference.2020

    • Author(s)
      Koga Y, Wei YH, Tanaka M.
    • Journal Title

      Biochem Biophys Acta-general

      Volume: 1864 Issue: 9 Pages: 129638-129638

    • DOI

      10.1016/j.bbagen.2020.129638

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arginine therapy in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes2020

    • Author(s)
      Ikawa M, Povalko N, Koga Y.
    • Journal Title

      Curr Opin Clin Nutr Metab Care

      Volume: 23 Issue: 1 Pages: 17-22

    • DOI

      10.1097/mco.0000000000000610

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biomarkers and clinical rating scales for sodium pyruvate therapy in patients with mitochondrial disease2019

    • Author(s)
      Koga Y, Povalko N, Inoue E, Nashiki K, Tanaka M.
    • Journal Title

      Mitochondrion

      Volume: 48 Pages: 11-15

    • DOI

      10.1016/j.mito.2019.02.001

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biomarker changes associated with clinical symptoms in MELAS patient2019

    • Author(s)
      Matsui M, Yamadera M, Saito T, Fujimura H, Sakoda S, Koga Y
    • Journal Title

      Neurol Clin Neurosci

      Volume: 7 Issue: 6 Pages: 344-346

    • DOI

      10.1111/ncn3.12325

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GDF-15, a mitochondrial disease biomarker, is associated with the severity of multiple sclerosis2019

    • Author(s)
      Nohara S, Ishii A, Yamamoto F, Yanagiha K, Moriyama T, Tozaka N, Miyake Z, Yatsuga S, Koga Y, Hosaka T, Terada M, Yamaguchi T, Aizawa S, Mamada N, Tsuji H, Tomidokoro Y, Nakamagoe K, Ishii K, Watanabe M, Tamaoka A
    • Journal Title

      Journal of the neurological sciences

      Volume: 405 Pages: 116429-116429

    • DOI

      10.1016/j.jns.2019.116429

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful treatment of infantile-onset ACAD9-related cardiomyopathy with a combination of sodium pyruvate, beta-blocker, and coenzyme Q102019

    • Author(s)
      Kadoya T, Sakakibara A, Kitayama K, Yamada Y, Higuchi S, Kawakita R, Kawasaki Y, Fujino M, Murakami Y, Shimura M, Murayama K, Ohtake A, Okazaki Y, Koga Y, Yorifuji T.
    • Journal Title

      J Pediatr Endocrinol Metab

      Volume: 32 Issue: 10 Pages: 1181-1185

    • DOI

      10.1515/jpem-2019-0205

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research2018

    • Author(s)
      Koga Y, Povalko N, Inoue E, Nakamura H, Ishii A, Suzuki Y, Yoneda M, Kanda F, Kubota M, Okada H, Fujii K.
    • Journal Title

      J Neurol

      Volume: 265 Issue: 12 Pages: 2861-2874

    • DOI

      10.1007/s00415-018-9057-7

    • NAID

      120007128515

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Temple syndrome diagnosed in an adult patient with clinical autism spectrum disorder2018

    • Author(s)
      Kimura T, Kagami M, Matsubara K, Yatsuga S, Mukasa R, Yatsuga C, Matsumoto T, Koga Y.
    • Journal Title

      Clinical Case Reports

      Volume: 7 Issue: 1 Pages: 15-18

    • DOI

      10.1002/ccr3.1895

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Mitochondrial biomarker GDF15: usefulness and development of diagnostic device from laboratory inspection to automated inspection2019

    • Author(s)
      Koga Y
    • Organizer
      Mitochondrial Medicine 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Clinical update: Treatment of mitochondrial disorders.2018

    • Author(s)
      Koga Y.
    • Organizer
      16th Conference of Asian Society for Mitochondrial Research and Medicine (ASMRM 2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Therapeutic regimen of L-arginine for MELAS and the development of new biomarker GDF15.2018

    • Author(s)
      Koga Y.
    • Organizer
      Symposium “Interactions: Dream”
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリア病のバイオマーカー2018

    • Author(s)
      八ツ賀秀一
    • Organizer
      第60回日本小児神経学会学術集会
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 危急疾患における予後を判定するためのバイオマーカー2021

    • Inventor(s)
      古賀靖敏
    • Industrial Property Rights Holder
      古賀靖敏
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-006020
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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