Development of new therapy for neuromyelitis optica using its animal models and anti-AQP4 antibodies.

• Project/Area Number: 16H05134
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Keio University
• Principal Investigator: Abe Yoichiro 慶應義塾大学, 医学部(信濃町), 講師 (10317331)
• Co-Investigator(Kenkyū-buntansha): 高井 良樹 東北大学, 大学病院, 医員 (40725743)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2018: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2016: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: アクアポリン４ / 視神経脊髄炎 / モノクローナル抗体 / 動物モデル / 抗体医薬 / 内在化／エンドサイトーシス / 自己免疫疾患 / 医療・福祉 / 薬理学 / 動物 / 脳神経疾患 / 免疫学 / 抗体製剤 / アストロサイト

Outline of Final Research Achievements

We planed to establish new animal models for developing new therapy for neuromyelitis optica.
In addition, we tried to elucidate a molecular mechanism for endocytosis of aquaporin-4 induced by binding of autoantibody called NMO-IgG. In this process, we found at least three amino-acid sequences responsible for endocytosis, intracellular trafficking, or degradation of aquaporin-4.

Academic Significance and Societal Importance of the Research Achievements

新しい視神経脊髄炎のモデル動物の作製のため、ラットの２系統を作製したことで、ラットにおけるゲノム編集技術の発展に寄与した。これらのラットの使用により、視神経脊髄炎治療法開発のためのツールが開発できただけでなく、他の疾患の治療法開発にも貢献できると期待される。また、体が小さいためにマウスでは困難であった研究を可能とする。これらラットはナショナルバイオリソースプロジェクトに寄託した。

Research Products

• [Journal Article] Aquaporin-4-dependent glymphatic solute transport in the rodent brain (2018)
  • Author(s): H. Mestre*, LM. Hablitz*, ALB. Xavier*, W. Feng*, W. Zou*, T. Pu*, H. Monai*, G. Murlidharan*, RM. Castellanos Rivera*, MJ. Simon*, MM. Pike*, V. Pla*, T. Du*, BT. Kress*, X. Wang, BA. Plog, AS. Thrane, I. Lundgaard, Y. Abe, M. Yasui, JH. Thomas, M. Xiao, H. Hirase, A. Asokan, JJ. Iliff, M. Nedergaard
  • Journal Title: eLife Volume: 7
  • DOI: 10.7554/elife.40070
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of diffusion-weighted MRI and anti-Stokes Raman scattering (CARS) measurements of the inter-compartmental exchange-time of water in expression-controlled aquaporin-4 cells (2018)
  • Author(s): Obata Takayuki、Kershaw Jeff、Tachibana Yasuhiko、Miyauchi Takayuki、Abe Yoichiro、Shibata Sayaka、Kawaguchi Hiroshi、Ikoma Yoko、Takuwa Hiroyuki、Aoki Ichio、Yasui Masato
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 17954-17954
  • DOI: 10.1038/s41598-018-36264-9
  • Peer Reviewed / Open Access
• [Journal Article] The Dual Effects of the Astrocyte-Specific Enhancer of the AQP4 M1 Promoter. (2017)
  • Author(s): Abe Yoichiro、Goda Wakami、Ikeshima-Kataoka Hiroko、Yasui Masato
  • Journal Title: FEBS Letters Volume: 591 Issue: 23 Pages: 3906-3915
  • DOI: 10.1002/1873-3468.12910
  • Peer Reviewed / Open Access
• [Presentation] Three amino-acid sequences regulate the expression level of aquaporin-4 (2019)
  • Author(s): Abe Y., Suzuki R., Goda W., and Yasui M.
  • Organizer: The 92nd Annual Meeting of the Japanese Pharmacological Society
• [Presentation] Development of a new Neuromyelitis Optica model mice. (2018)
  • Author(s): Chau S.H., Abe Y., and Yasui, M.
  • Organizer: The 18th World Congress of Basic and Clinical Pharmacology/The 91st Annual Meeting of the Japanese Pharmacological Society
  • Int'l Joint Research
• [Presentation] Identification of regions in the C-terminal domain of aquaporin-4 responsible for its intracellular trafficking and degradation. (2018)
  • Author(s): Abe Y., Suzuki R., Goda W., and Yasui M.
  • Organizer: The 41st Annual Meeting of the Molecular Biology Society of Japan
• [Presentation] Roles of the C-terminal domain in intracellular trafficking and degradation of AQP4. (2017)
  • Author(s): Abe, Y., Fujii, A., Goda, W., and Yasui, M.
  • Organizer: The 40th Annual Meeting of the Molecular Biology Society of Japan
• [Remarks] 慶應義塾大学 研究者情報総覧
  • URL: http://k-ris.keio.ac.jp/Profiles/54/0005317/profile.html
• [Remarks] Keio Researchers Information System
  • URL: https://keio.pure.elsevier.com/ja/persons/yoichiro-abe