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January 2023; 10 (1) Research ArticleOpen Access

Sustained Low Relapse Rate With Highly Variable B-Cell Repopulation Dynamics With Extended Rituximab Dosing Intervals in Multiple Sclerosis

View ORCID ProfileChiara Starvaggi Cucuzza, Elisa Longinetti, Nicolas Ruffin, Björn Evertsson, View ORCID ProfileIngrid Kockum, Maja Jagodic, Faiez Al Nimer, Thomas Frisell, View ORCID ProfileFredrik Piehl
First published November 21, 2022, DOI: https://doi.org/10.1212/NXI.0000000000200056
Chiara Starvaggi Cucuzza
From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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  • ORCID record for Chiara Starvaggi Cucuzza
Elisa Longinetti
From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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Nicolas Ruffin
From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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Björn Evertsson
From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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Ingrid Kockum
From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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  • ORCID record for Ingrid Kockum
Maja Jagodic
From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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Faiez Al Nimer
From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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Thomas Frisell
From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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Fredrik Piehl
From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
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  • ORCID record for Fredrik Piehl
Full PDF
Citation
Sustained Low Relapse Rate With Highly Variable B-Cell Repopulation Dynamics With Extended Rituximab Dosing Intervals in Multiple Sclerosis
Chiara Starvaggi Cucuzza, Elisa Longinetti, Nicolas Ruffin, Björn Evertsson, Ingrid Kockum, Maja Jagodic, Faiez Al Nimer, Thomas Frisell, Fredrik Piehl
Neurol Neuroimmunol Neuroinflamm Jan 2023, 10 (1) e200056; DOI: 10.1212/NXI.0000000000200056

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Article Information

vol. 10 no. 1 e200056
DOI: 
https://doi.org/10.1212/NXI.0000000000200056
PubMed: 
36411076

Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received May 10, 2022
  • Accepted in final form September 16, 2022
  • First Published November 21, 2022.

Copyright & Usage: 
Copyright © 2022 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 License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Author Disclosures

    1. Chiara Starvaggi Cucuzza, MD,
    2. Elisa Longinetti, PhD,
    3. Nicolas Ruffin, PhD,
    4. Björn Evertsson, MD,
    5. Ingrid Kockum, PhD,
    6. Maja Jagodic, PhD,
    7. Faiez Al Nimer, MD, PhD,
    8. Thomas Frisell, PhD and
    9. Fredrik Piehl, MD, PhD
  1. Chiara Starvaggi Cucuzza, MD,
  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

  3. Elisa Longinetti, PhD,
  4. 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. The Swedish Research Council for Health, Working Life, and Welfare (postdoc Grant No: 2020-0115 to E.L.)

    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. Nicolas Ruffin, PhD,
  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. (1) Swedish StromaBio AB,

    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. (1) Knut and Alice Wallenberg foundation, (2) NEURO Sweden, (3) MS forskningsfonden (4) Svenska Läkaresällskapets fonder SLS-961723,

    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. Björn Evertsson, MD,
  8. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. Travel grant from Roche for ECTRIMS 2018.

    Editorial Boards:
    1. NONE

    Patents:
    1. NONE

    Publishing Royalties:
    1. NONE

    Employment, Commercial Entity:
    1. NONE

    Consultancies:
    1. (1)Consultancies fees from Roche for writing a summery of ECTRIMS 2018.

    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. Ingrid Kockum, PhD,
  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. 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. Stockholm county council (2018-2019) 800 000 SEK, 600 000 (2020-2021), SEK 1 750 000 (2022-2024)Karolinska Insitutet (2015-2020) PhD student funding 1 080 000 SEKEU Horizon 2020: MultipleMS consortium (2017-2021). Amount for whole consortium: 14,700 000 EURO, Share for my research group: 18 000 000 SEK EU Horizon 2020: EU STANDS-4PM consortium (2019-2021). Share for my research group: 61 875 EUROSwedish research council (2021-2024) SEK 4 800 000

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. 100 year fonden at Karolinska Univiersity hospital during 2016 (150 000 SEK), "Hjärnfonden" during 2016, 2020-2023 as principal investigator (500 000, 600 00/year SEK respectively), Åke Löwnertz Stiftelse för Neurologisk Forskning 2018 (100 000 SEK). I have also received funding from Magareta af Ugglas Foundation (2015-2025) and PCORI (2017-2025) as co applicant.

    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. I and my mother have held stocks in a number of mainly Swedish companies. None of them are related to this study. Only one of them is involved medical research: Novo Nordisk which my mother has shares in.

    Legal Proceedings:
    1. NONE

    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. Stockholm county council (2018-2019) 800 000 SEK, 600 000 (2020-2021), SEK 1 750 000 (2022-2024)Karolinska Insitutet (2015-2020) PhD student funding 1 080 000 SEKEU Horizon 2020: MultipleMS consortium (2017-2021). Amount for whole consortium: 14,700 000 EURO, Share for my research group: 18 000 000 SEK EU Horizon 2020: EU STANDS-4PM consortium (2019-2021). Share for my research group: 61 875 EUROSwedish research council (2021-2024) SEK 4 800 000

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. 100 year fonden at Karolinska Univiersity hospital during 2016 (150 000 SEK), "Hjärnfonden" during 2016, 2020-2023 as principal investigator (500 000, 600 00/year SEK respectively), Åke Löwnertz Stiftelse för Neurologisk Forskning 2018 (100 000 SEK). I have also received funding from Magareta af Ugglas Foundation (2015-2025) and PCORI (2017-2025) as co applicant.

    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. I and my mother have held stocks in a number of mainly Swedish companies. None of them are related to this study. Only one of them is involved medical research: Novo Nordisk which my mother has shares in.

    Legal Proceedings:
    1. NONE

  11. Maja Jagodic, PhD,
  12. Scientific Advisory Boards:
    1. None

    Gifts:
    1. NONE

    Funding for Travel or Speaker Honoraria:
    1. None

    Editorial Boards:
    1. (1) Physiological Genomics, Editorial Board member, 2015-2021(2) Frontiers in Neurology, Associate Editor, 2017-present(3) Scientific Reports, Editorial Board member, 2018-present

    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. (1) European Union’s Innovative Medicines Initiative 2, EUbOPEN (875510), co-investigator, 2020-2025(2) European Research Council (ERC) Consolidator Grant, Epi4MS (818170), lead investigator, 2019-2024(3) Swedish Research Council, (2018-02638), lead investigator, 2019-2022(4) Karolinska Institutet's funds, KID, lead investigator, 2019-2023(5) European Union’s Horizon 2020 Research and Innovation Programme, MultipleMS (733161), co-lead investigator, 2017-2022(6) Stockholm County Council, ALF project (20200278), lead investigator, 2021-2022

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. (1) The Knut and Alice Wallenberg Foundation, (2019-0089), lead investigator, 2020-2024(2) The Brain Foundation (Hjärnfonden), (FO2021-0150), lead investigator, 2021-2024

    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

  13. Faiez Al Nimer, MD, PhD,
  14. 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. (1) Swedish Brain foundation (2) Neuro Sweden

    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

  15. Thomas Frisell, PhD and
  16. 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. The Swedish Research Council (DNR 2016-01355)

    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

  17. Fredrik Piehl, MD, PhD
  18. Scientific Advisory Boards:
    1. Data safety monitoring board member in studies with Roche and Lundbeck

    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. (1) Janssen - academic research support relevant to this topic(2) Merck KGaA -academic research support relevant to this topic(1) UCB - academic research support outside of this topic

    Research Support, Government Entities:
    1. (1) Swedish Medical Research Council (grant 2020-02700) PI, 2020-ongoing.(2) Pcori, Washington DC (grant MS-1511-33196) PI, 2017-ongoing(3) European Union’s Horizon 2020 Research and Innovation Programme (MultipleMS, EU RIA 733161), co-investigator, 2017-ongoing

    Research Support, Academic Entities:
    1. (1) Stockholm County (grant 20200451), PI, 2020-ongoing.

    Research Support, Foundations and Societies:
    1. (1) the Knut and Alice Wallenberg Foundation(2) Hjärnfonden (grant FO2021-0277)

    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. Novartis, expert witness statement, 2020-2021.

  1. From the Department of Clinical Neuroscience (C.S.C., E.L., N.R., B.E., I.K., M.J., F.A.N., F.P.), Karolinska Institutet, Stockholm, Sweden; Center for Molecular Medicine (C.S.C., N.R., I.K., M.J., F.A.N., F.P.), Karolinska University Hospital, Stockholm, Sweden; Department of Neurology (B.E., F.P.), Karolinska University Hospital, Stockholm, Sweden; Center for Neurology (C.S.C., I.K., M.J., F.A.N., F.P.), Academic Specialist Center, Stockholm, Sweden; and Clinical Epidemiology Division (T.F.), Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
  1. Correspondence
    Dr. Piehl fredrik.piehl{at}ki.se
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