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November 2021; 8 (6) ArticleOpen Access

New BBB Model Reveals That IL-6 Blockade Suppressed the BBB Disorder, Preventing Onset of NMOSD

Yukio Takeshita, Susumu Fujikawa, Kenichi Serizawa, Miwako Fujisawa, Kinya Matsuo, Joe Nemoto, Fumitaka Shimizu, Yasuteru Sano, Haruna Tomizawa-Shinohara, Shota Miyake, Richard M. Ransohoff, Takashi Kanda
First published October 19, 2021, DOI: https://doi.org/10.1212/NXI.0000000000001076
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Article Information

vol. 8 no. 6 e1076
DOI: 
https://doi.org/10.1212/NXI.0000000000001076
PubMed: 
34667128
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received January 28, 2021
  • Accepted in final form June 24, 2021
  • First Published October 19, 2021.
Copyright & Usage: 
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Author Disclosures

    1. Yukio Takeshita, MD, PhD* (takeshy{at}yamaguchi-u.ac.jp),
    2. Susumu Fujikawa, MD* (smfujika{at}yamaguchi-u.ac.jp),
    3. Kenichi Serizawa, PhD (serizawakni{at}chugai-pharm.co.jp),
    4. Miwako Fujisawa, MD (fuji0418{at}yamaguchi-u.ac.jp),
    5. Kinya Matsuo, MD (matsuok{at}yamaguchi-u.ac.jp),
    6. Joe Nemoto, MD (nemoto{at}yamaguchi-u.ac.jp),
    7. Fumitaka Shimizu, MD, PhD (fshimizu{at}yamaguchi-u.ac.jp),
    8. Yasuteru Sano, MD, PhD (yasuteru{at}yamaguchi-u.ac.jp),
    9. Haruna Tomizawa-Shinohara, PhD (shinohara.haruna89{at}chugai-pharm.co.jp),
    10. Shota Miyake (miyake.shota34{at}chugai-pharm.co.jp),
    11. Richard M. Ransohoff, MD, PhD (rransohoff{at}thirdrockventures.com) and
    12. Takashi Kanda, MD, PhD
  1. Yukio Takeshita, MD, PhD* (takeshy{at}yamaguchi-u.ac.jp),
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Susumu Fujikawa, MD* (smfujika{at}yamaguchi-u.ac.jp),
    3. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Kenichi Serizawa, PhD (serizawakni{at}chugai-pharm.co.jp),
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. (1) Filing a patent application(PCT/JP2020/005965; (Inhibitory effect of anti-IL-6 receptor antibody on BBB dysfunction)

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. (1)Chugai Pharmaceutical Co., Ltd., general employee, 14 years

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. I am employee of Chugai Pharmaceutical Co., Ltd. So our research was funded from Chugai Pharmaceutical Co., Ltd. departmental resources.

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Miwako Fujisawa, MD (fuji0418{at}yamaguchi-u.ac.jp),
    5. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Kinya Matsuo, MD (matsuok{at}yamaguchi-u.ac.jp),
    6. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Joe Nemoto, MD (nemoto{at}yamaguchi-u.ac.jp),
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Fumitaka Shimizu, MD, PhD (fshimizu{at}yamaguchi-u.ac.jp),
    8. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Biogen, postdoctoral scientist, 1 years 10 month(2014.11- 2016.8)

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  8. Yasuteru Sano, MD, PhD (yasuteru{at}yamaguchi-u.ac.jp),
    9. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  9. Haruna Tomizawa-Shinohara, PhD (shinohara.haruna89{at}chugai-pharm.co.jp),
    10. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. (1)Chugai Pharmaceutical Co., LTD., general employee. 6 years

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. I am employee of Chugai Pharmaceutical Co., LTD. So our research was funded from Chugai Pharmaceutical Co., LTD. departmental resource.

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  10. Shota Miyake (miyake.shota34{at}chugai-pharm.co.jp),
    11. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. (1) Chugai Pharmaceutical co., Ltd., general employee, 2 years

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. I am employee of Chugai Pharmaceutical Co., Ltd. So our research was funded from Chugai Pharmaceutical Co., Ltd. departmental resources.

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  11. Richard M. Ransohoff, MD, PhD (rransohoff{at}thirdrockventures.com) and
    12. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. Employed at present by Third Rock Ventures as Venture Partner. This work is unrelated to my employment at Third Rock Ventures.

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. Chemocentryx, exercise and sell stock options Stock/Stock Options, Medical Equipment & Materials: Third Rock Ventures, Fund V and related portfolio companies

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  12. Takashi Kanda, MD, PhD
    13. Scientific Advisory Boards:

    1. (1) CSL Behring (2) Chugai Paharmaceutical Co.

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Novartis Pharma Co, speaker honararia (2) Otsuka Pharmaceutical, speaker honararia (3) Ayumi Pharmaceutical, speaker honararia (4) Japan Blood, speaker honararia (5) Takeda Pharmacuetical Co., speaker honararia (6) Kyowa-Kirin Pharmaceutical Co., speaker honararia (7) Dainipponsumitomo Pharmaceutical Co., speaker honararia (8) Tanabe Mitsubishi Pharmaceutical Co., speaker honararia (9) CSL Behring,, speaker honararia (10) Janssen Pahrmaceutical Co., speaker honararia (11) Teijin Pharm., speaker honararia (12) Biogen Japan, speaker honararia (13) Eosai Pharmaceutical, speaker honararia (14) Alexion Pharm., speaker honararia (15) Glaxo Smith Klein, , speaker honararia (16) Ono Pharmaceutical Co., speaker honararia

    Editorial Boards:

    1. (1) Clinical and Experimental Neuroimmunology Editor-in- Chief 2010-2018 (2) Neuropathology, Editorial Advisory Board Member 2009- (3) Brain and Nerve Editor-in-Chief 2018- (4) Peripheral Nerve, Editor-in-Chief, 2017-2021 (5) Fluids and Barriers of the CNS, Editor 2014-

    Patents:

    1. (1) in vitro model of blood-brain barrier

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Teijin pharmaceutical Co.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Novartis Pharm. (2) Daiichi-Sankyo Co. (3) Asteras Co.

    Research Support, Government Entities:

    1. (1) Contract Grant Sponsor: Japan Society for the Promotion of Science - Tokyo Contract Grant Number: 25293203, 26670443, 17H04197

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  1. From the Department of Neurology and Clinical Neuroscience (Y.T., S.F., M.F., K.M., J.N., F.S., Y.S., T.K.), Yamaguchi University Graduate School of Medicine; Kenichi Serizawa (K.S., H.T.-S., S.M.), Haruna Tomizawa-Shinohara and Shota Miyake, Product Research Department, Chugai Pharmaceutical Co., Ltd, Kanagawa, Japan; and Richard M Ransohoff (R.M.R.), Third Rock Ventures, Boston, MA.
  1. Correspondence
    Dr. Kanda tkanda{at}yamaguchi-u.ac.jp
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