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Development of a novel therapeutic strategy to recover the laryngeal function after recurrent laryngeal nerve injury

Research Project

Project/Area Number 21K09597
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionNational Defense Medical College

Principal Investigator

Araki Koji  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 耳鼻咽喉科学, 教授 (70317220)

Co-Investigator(Kenkyū-buntansha) 宇野 光祐  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 病院 耳鼻咽喉科, 講師 (20464828)
塩谷 彰浩  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 耳鼻咽喉科学, 教授 (80215946)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords反回神経 / 喉頭機能 / 神経障害 / 過誤神経再生 / 遺伝子治療
Outline of Research at the Start

神経機能再生には①神経線維再生不良、②中枢における運動神経細胞死、③末梢筋における運動終板の変性、④筋組織の萎縮変性、⑤過誤神経再生、の問題点を解決する必要があり、申請者らは①-④についてはこれまでに解決策を見出してきた。本研究では⑤過誤神経再生の克服による機能回復を目指した新規治療法の開発を目指す。
唯一の声門開大筋である後輪状披裂筋への運動神経線維再生を促す神経栄養因子を明らかにし、その阻害により声門閉鎖筋への再生を促す、かつ/または声門閉鎖筋群への運動神経線維再生を促し声門閉鎖筋への再生を促進し、声門閉鎖機能回復を目指した治療戦略開発を進める。

Outline of Final Research Achievements

This study aimed to recover laryngeal function in recurrent laryngeal nerve disorders. We aimed to strengthen glottal closure by using a nerve regeneration tube used in clinical practice, as well as neurotrophic factors. We identified a neurotrophic factor that promotes motor nerve fiber regeneration to the posterior cricoarytenoid muscle, the only glottal opener muscle.And we developed a treatment strategy to inhibit motor nerve regeneration to the posterior cricoarytenoid muscle by inhibiting this factor, thereby recovering glottal closure function. We also established a rat posterior cricoarytenoid muscle branch amputation model and a vocal cord movement evaluation system, examined the effect of enhancing vocal cord closure function in a rat posterior cricoarytenoid muscle branch amputation model, and examined the factors that inhibit motor nerve regeneration in the posterior cricoarytenoid muscle, ultimately attempting to develop a treatment that can be applied clinically.

Academic Significance and Societal Importance of the Research Achievements

耳鼻咽喉科臨床においてしばしば問題となる反回神経障害は、呼吸・発声・嚥下の障害をきたし、患者のQOLを著しく低下させる。喉頭機能回復における最大の障害である過誤神経再生克服による新規治療法の開発を行っている。反回神経運動線維間での過誤再生を可能な限り抑制し、声門閉鎖機能再生の改善を目指した研究であり、既に臨床で用いられている神経再生チューブや遺伝子治療などの先進的技術を応用し、最終的には臨床応用可能な治療法開発を目指している。本研究自体は反回神経障害を標的としているが、他領域の末梢神経障害にも広く応用可能な治療法開発であり、汎用性や発展性の非常に高い研究である。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (24 results)

All 2024 2023 2022 2021

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (16 results) (of which Int'l Joint Research: 6 results,  Invited: 9 results)

  • [Journal Article] 喉頭部分切除術の適応と実際2024

    • Author(s)
      荒木 幸仁
    • Journal Title

      Nippon Jibiinkoka Tokeibugeka Gakkai Kaiho(Tokyo)

      Volume: 127 Issue: 2 Pages: 83-91

    • DOI

      10.3950/jibiinkotokeibu.127.2_83

    • ISSN
      2436-5793, 2436-5866
    • Year and Date
      2024-02-20
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 特集 小児の耳鼻咽喉・頭頸部手術-保護者への説明のコツから術中・術後の注意点まで〔特別付録Web動画〕 《咽頭・喉頭・頸部領域手術》 気道異物摘出術/食道異物摘出術2023

    • Author(s)
      宇野 光祐、荒木 幸仁
    • Journal Title

      耳鼻咽喉科・頭頸部外科

      Volume: 95 Issue: 9 Pages: 732-737

    • DOI

      10.11477/mf.1411203459

    • ISSN
      0914-3491, 1882-1316
    • Year and Date
      2023-08-20
    • Related Report
      2023 Annual Research Report
  • [Journal Article] A case of airway emergency due to deep neck infection treated by oral intubation without tracheostomy: Is tracheostomy essential in the treatment of deep neck abscesses?2023

    • Author(s)
      Takenaka Tatsuya, Mizokami Daisuke, Takihata Saki, Araki Koji, Shiotani Akihiro.
    • Journal Title

      Journal of hospital general medicine

      Volume: 5 Pages: 21-24

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Delayed postoperative bleeding associated with laryngopharyngeal necrosis following salvage endoscopic laryngopharyngeal surgery for recurrent adenoid cystic carcinoma of the tongue base after carbon ion radiotherapy: Case report.2023

    • Author(s)
      Hiroya Yonaga, Kosuke Uno, Shinichi Taniai, Masahiko Seki, Naoki Matsuno, Akihiro Shiotani, Koji Araki.
    • Journal Title

      Acta Oto-Laryngologica Case Reports

      Volume: 8 Pages: 1-1

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Injection Laryngoplasty for Unilateral Vocal Fold Paralysis2023

    • Author(s)
      Araki Koji、Uno Kosuke、Shiotani Akihiro
    • Journal Title

      Practica Oto-Rhino-Laryngologica

      Volume: 116 Issue: 10 Pages: 933-942

    • DOI

      10.5631/jibirin.116.933

    • ISSN
      0032-6313, 1884-4545
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The value of serum p53 antibody as a biomarker in oral and pharyngeal squamous cell carcinoma2023

    • Author(s)
      Hirokawa Shotaro、Araki Koji、Yamashita Taku、Uno Kosuke、Tomifuji Masayuki、Shimada Hideaki、Shiotani Akihiro
    • Journal Title

      Acta Oto-Laryngologica

      Volume: 143 Issue: 1 Pages: 85-90

    • DOI

      10.1080/00016489.2023.2165144

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of chronological changes in videofluorographic findings after transoral videolaryngoscopic surgery to reveal mechanism of dysphagia2023

    • Author(s)
      Kimura Eiko、Tomifuji Masayuki、Uno Kosuke、Taniai Shinichi、Araki Koji、Shiotani Akihiro
    • Journal Title

      Auris Nasus Larynx

      Volume: 50 Issue: 3 Pages: 374-382

    • DOI

      10.1016/j.anl.2022.08.005

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 咽喉頭疾患に対する経口的咽喉頭部分切除術2022

    • Author(s)
      荒木幸仁
    • Journal Title

      防衛医大雑誌

      Volume: 47 Pages: 168-175

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Presentation] シンポジウム2 「喉頭・気管基礎研究からのイノベーション創出」喉頭機能回復を目指した反回神経再生への取り組み.2024

    • Author(s)
      荒木幸仁、宇野光祐、鈴木洋、関雅彦、平野正大、塩谷彰浩.
    • Organizer
      第36回日本喉頭科学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Transoral videolayngoscopic vocal fold medialization with calcium phosphate cement for unilateral vocal cord palsy – Experience of original technique.2023

    • Author(s)
      Seki Masahiko, Uno Kosuke , Shiotani Akihiro, Araki Koji.
    • Organizer
      The 13th East Asian Conference on Phonosurgery (EACP 2023), Miyagi, Japan, July 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Value of expiratory resistance training (EMST) as a preoperative exercise for laryngopharyngeal cancer patients with transoral videolaryngoscopic surgery (TOVS).2023

    • Author(s)
      Taniai Shinichi, Araki Koji, Tomifuji Masayuki, Uno Kosuke, Shibamoto Isamu, Shiotani Akihiro.
    • Organizer
      32nd World congress of the IALP. Auckland, New Zealand, August 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Transoral endoscopic dilating and silicon-keel stenting for supraglottic stenosis.2023

    • Author(s)
      3)Kosuke Uno, Keiji Wada, Naoki Matsuno, Hideyuki Tsuboi, Akihiro Shiotani and Koji Araki.
    • Organizer
      The 16th Taiwan-Japan Conference on Otolaryngology-Head and Neck Surgery (16th TJCOHNS). Thaichung,Taiwan, December 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 【Symposium: Laryngology】 Basic Research for Functional Regeneration after Recurrent Laryngeal Nerve Injury.2023

    • Author(s)
      Koji Araki.
    • Organizer
      The 16th Taiwan-Japan Conference on Otolaryngology Otolaryngology-Head and Neck Surgery, Thaichung,Taiwan, December 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 【手術手技セミナー】喉頭機能温存を目指した喉頭部分切除術.2023

    • Author(s)
      荒木幸仁
    • Organizer
      第124回日本耳鼻咽喉科頭頸部外科学会. 福岡 5月
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 【パネルディスカッション】どうする!音声外科手術.2023

    • Author(s)
      荒木幸仁.
    • Organizer
      第68 回日本音声言語医学会. 岡山 10月
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 【領域講習】咽喉頭疾患に対する機能温存を目指した外科的治療.2023

    • Author(s)
      荒木 幸仁.
    • Organizer
      第143回日耳鼻埼玉県地方部会学術講演会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 【特別企画ワークショップ8】「どうする?がん治療の後遺障害 -再建手術のススメ-」 反回神経障害に伴う音声障害、嚥下障害に対する機能再建手術.2023

    • Author(s)
      荒木 幸仁
    • Organizer
      第61回日本癌治療学会学術集会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Oncolytic Sendai virus as a novel treatment option for head and neck squamous cell carcinoma.2022

    • Author(s)
      Matsuno Naoki, Araki Koji, Tanaka Shingo, Miyagawa Yoshihiro, Tanaka Yuya, Tomifuji Masayuki, Uno Kosuke, Yamashita Taku, Ueda Yasuji, Inoue Makoto, Shiotani Akihiro
    • Organizer
      The 14th International Oncolytic Virotherapy Conference
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Basic research for functional regeneration after recurrent laryngeal nerve injury.2022

    • Author(s)
      Araki Koji
    • Organizer
      International Association of Phonosurgery 2022
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Transoral videolayngoscopic vocal fold medialization with calcium phosphate cement for unilateral vocal cord palsy - Value of novel technique.2022

    • Author(s)
      Uno Kosuke, Araki Koji, Tomifuji Masayuki, Shiotani Akihiro
    • Organizer
      International Association of Phonosurgery 2022
    • Related Report
      2022 Research-status Report
  • [Presentation] Robotic & Minimal Invasive Surgery - Transoral Vidiolaryngoscopic Surgery (TOVS) for Laryngopharyngeal Cancer.2022

    • Author(s)
      Araki Koji
    • Organizer
      The 1st Joint meeting of Tri-Head and Neck Society,
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 咽喉頭疾患に対する低侵襲手術の展望2022

    • Author(s)
      荒木幸仁.
    • Organizer
      第35 回日本口腔・咽頭科学会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 頭頸部扁平上皮癌患者における血清 PD-L1 の診断・予後バイオマーカーとしての有用性.2022

    • Author(s)
      廣川祥太郎, 荒木 幸仁, 宇野光祐, 松野直樹, 塩谷 彰浩.
    • Organizer
      第46 回頭頸部癌学会総会・学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] Inhibition of Extracellular signal-regulated kinase pathway suppresses tracheal stenosis.2021

    • Author(s)
      Akari Kimura, Koji Araki, Yasushi Sato, Sachiyo Mogi, Kazuko Fujitani, Takaomi Kurioka, Shogo Endo, Akihiro Shiotani, Taku Yamashita.
    • Organizer
      13th Congress of the European Laryngological Society
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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