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Elucidation of pathophysiology and development of blood biomarkers focusing on lipid metabolism in interstitial cystitis

Research Project

Project/Area Number 20K09566
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionNara Medical University

Principal Investigator

Torimoto Kazumasa  奈良県立医科大学, 医学部, 准教授 (10382293)

Co-Investigator(Kenkyū-buntansha) 藤本 清秀  奈良県立医科大学, 医学部, 教授 (50264867)
可野 邦行  東京大学, 大学院薬学系研究科(薬学部), 助教 (50636404)
Project Period (FY) 2020-04-01 – 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 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords間質性膀胱炎 / 膀胱痛症候群 / 血液バイオマーカー / リノール酸 / アナンダミド / バイオマーカー / リゾリン脂質
Outline of Research at the Start

間質性膀胱炎・膀胱痛症候群診療(IC/BPS)は病態が未解明で、診断基準および治療が確立されていない難病である。客観的指標がないため、診断に豊富な経験が必要である。国内外で尿または血液バイオマーカー研究が行われてきたが、未だ臨床応用に至っていない。本研究では、網羅的探索で得られた血液バイオマーカー候補(リゾリン脂質など)について有用性の検証を進めるとともに、脂質代謝を中心に解析してIC/BPSの病態解明を目指す。血液バイオマーカーが完成すれば、診断が容易となりドクターショッピングを回避できる。また、複数の病態が混在するIC/BPS患者をバイオマーカーで均質化し、治療薬開発に貢献できる。

Outline of Final Research Achievements

We enrolled patients with Hunner-type interstitial cystitis (HIC) (n=20), bladder pain syndrome (BPS) (n=20), and overactive bladder (OAB) (n=20) and without lower urinary tract symptoms (controls, n=15). Metabolomics was performed on 323 serum metabolites using liquid chromatography time-of-flight mass spectrometry.
The relative areas including anandamide, acylcarnitine (18:2), linoleoyl ethanolamide, and arachidonic acid were smaller in the HIC or BPS group than in the OAB or control group. The differences in the relative areas of anandamide were significant (median: 3.950e-005 and 4.150e-005 vs. 8.300e-005 and 9.800e-005), and the ability to discriminate IC/BPS exhibited an area under the curve of 0.9321.
Serum anandamide may be a feasible diagnostic biomarker for IC/BPS. Low serum anandamide levels might be associated with pain and inflammation initiation and may reflect the pathology of IC/BPS.

Academic Significance and Societal Importance of the Research Achievements

間質性膀胱炎・膀胱痛症候群(IC/BPS)の病態は解明されておらず、診断ならびに治療は確立されていない。診断は、尿意亢進や頻尿などの下部尿路症状を呈する、混同しうる疾患を除外した上で、IC/BPSを疑い、痛みなど強い症状の要因であるハンナ病変の有無を膀胱鏡で確認するという過程である。これには十分な経験が必要で、実臨床では診断が難しい。我々が見出した血清アナンダミドをバイオマーカーとして用いれば、診断における大きな補助となる。また、診断精度の向上は、IC/BPSの病態解明ならびに治療方法開発の促進に寄与する。

Report

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

    (8 results)

All 2023 2022 2021 2020

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 2 results)

  • [Journal Article] Identification of diagnostic serum biomarkers for Hunner-type interstitial cystitis2022

    • Author(s)
      Kazumasa Torimoto, Tomohiro Ueda, Masato Kasahara, Akihide Hirayama, Chie Matsushita, Yoshihiro Matsumoto, Daisuke Gotoh, Yasushi Nakai, Makito Miyake, Katsuya Aoki, Kiyohide Fujimoto
    • Journal Title

      Lower Urinary Tract Symptoms

      Volume: Online ahead of print Issue: 5 Pages: 334-340

    • DOI

      10.1111/luts.12439

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Serum anandamide and lipids associated with linoleic acid can distinguish interstitial cystitis and bladder pain syndrome from overactive bladder2023

    • Author(s)
      Torimoto K, Ueda T, Gotoh D, Kano K, Miyake M, Nakai Y, Hori S, Morizawa Y, Onishi K, Shimizu T, Tomizawa M, Aoki J, Fujimoto K
    • Organizer
      第110回日本排尿機能学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Serum anandamide and lipids associated with linoleic acid can distinguish interstitial cystitis and bladder pain syndrome from overactive bladder2023

    • Author(s)
      Torimoto K, Ueda T, Gotoh D, Kano K, Miyake M, Nakai Y, Hori S, Morizawa Y, Onishi K, Shimizu T, Tomizawa M, Aoki J, Fujimoto K
    • Organizer
      The Annual Meeting of American Urological Association 2023
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 間質性膀胱炎・膀胱痛症候群の血液検査診断をめざす研究2020

    • Author(s)
      鳥本一匡、上田朋宏、笠原正登、平山暁秀、松下千枝、松本吉弘、三宅牧人、田中宣道、藤本清秀
    • Organizer
      第108回日本泌尿器科学会総会
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 間質性膀胱炎/膀胱痛症候群の診断方法2023

    • Inventor(s)
      鳥本一匡、上田朋宏、藤本清秀
    • Industrial Property Rights Holder
      鳥本一匡、上田朋宏、藤本清秀
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2023-060523
    • Filing Date
      2023
    • Related Report
      2022 Annual Research Report
  • [Patent(Industrial Property Rights)] Method for Diagnosing Interstitial Cystitis2021

    • Inventor(s)
      Torimoto K, Fujimoto K, Ueda T
    • Industrial Property Rights Holder
      Torimoto K, Fujimoto K, Ueda T
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] Method for Diagnosing Interstitial Cystitis2020

    • Inventor(s)
      鳥本一匡、藤本清秀、上田朋宏
    • Industrial Property Rights Holder
      鳥本一匡、藤本清秀、上田朋宏
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 間質性膀胱炎の診断方法2020

    • Inventor(s)
      鳥本一匡、藤本清秀、上田朋宏
    • Industrial Property Rights Holder
      鳥本一匡、藤本清秀、上田朋宏
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Acquisition Date
      2020
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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