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July 2020; 7 (4) ArticleOpen Access

Detecting and predicting neutralization of alemtuzumab responses in MS

Gauri Saxena, James M. Moore, Meleri Jones, Gareth Pryce, Liaqat Ali, Georgia R. Leisegang, Vivek Vijay, Samantha Loveless, Neil P. Robertson, Klaus Schmierer, Gavin Giovannoni, Sharmilee Gnananpavan, David Baker, Emma C. Tallantyre, Angray S. Kang
First published June 4, 2020, DOI: https://doi.org/10.1212/NXI.0000000000000767
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Article Information

vol. 7 no. 4 e767
DOI: 
https://doi.org/10.1212/NXI.0000000000000767
PubMed: 
32499328
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received January 10, 2020
  • Accepted in final form April 13, 2020
  • First Published June 4, 2020.
Copyright & Usage: 
Copyright © 2020 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. Gauri Saxena, BSc*,
    2. James M. Moore, MBBS*,
    3. Meleri Jones, PhD,
    4. Gareth Pryce, PhD,
    5. Liaqat Ali, PhD,
    6. Georgia R. Leisegang, MSc,
    7. Vivek Vijay, MBBS,
    8. Samantha Loveless, PhD,
    9. Neil P. Robertson, MD,
    10. Klaus Schmierer, PhD,
    11. Gavin Giovannoni, PhD,
    12. Sharmilee Gnananpavan, PhD,
    13. David Baker, PhD,
    14. Emma C. Tallantyre, PhD* and
    15. Angray S. Kang, PhD*
  1. Gauri Saxena, BSc*,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Rod Flower Summer Scholarship awarded by QMUL

    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. James M. Moore, MBBS*,
    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. Meleri Jones, 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. 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. Gareth Pryce, PhD,
    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. National Multiple Sclerosis Society

    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. Liaqat Ali, 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. 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. National University of Medical Sciences, Rawalpindi, Pakistan.

    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. Georgia R. Leisegang, MSc,
    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. Vivek Vijay, MBBS,
    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. 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

  8. Samantha Loveless, PhD,
    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. Neil P. Robertson, MD,
    10. Scientific Advisory Boards:

    1. Professor Robertson has served on Advisory boards for Genzyme, Roche, Novartis, Biogen, Celgene

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Professor Robertson has recieved honoraria for speaking at academic meetings from Biogen and Genzyme

    Editorial Boards:

    1. Professor robertson serves as an editor for the Journal of Neurology since 2012

    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. Neuroimmunology Fellowship Genzyme Mortality of MS Novartis pidemiology of MS, Novartis

    Research Support, Government Entities:

    1. National institute of Heath Wales, co-applicant 2015-18

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Medical Research Council UK Welcome Trust

    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. Klaus Schmierer, PhD,
    11. Scientific Advisory Boards:

    1. (i) Novartis (ii) Merck KG Aa (iii) Roche

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (i) Novartis, speaker honoraria (ii) Biogen, speaker honoraria (iii) Teva, speaker honoraria (iv) Merck KG Aa, speaker honoraria (v) Sanofi-Genzyme, speaker honoraria (vi) Roche, speaker honoraria

    Editorial Boards:

    1. MS Reports, editorial board, since Jun 2014

    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

  11. Gavin Giovannoni, PhD,
    12. Scientific Advisory Boards:

    1. (1) AbbVie, (2)Actelion, (3) Biogen, (4) Celgene, (5)Sanofi-Genzyme, (6) Genentech, (7) GlaxoSmithKline, (8) Merck-Serono, (9) Novartis, (10) Roche and (11) Teva.

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Speaker honoraria: (1) AbbVie, (2) Actelion, (3) Biogen, (4) Celgene, (5) Sanofi-Genzyme, (6) Genentech, (7) Merck-Serono, (8) Novartis, (9) Roche and (10) Teva.

    Editorial Boards:

    1. (1) Multiple Sclerosis and Related Disorders, Editor since 2011

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) AbbVie, (2) Actelion, (3) Atara Bio, (4) Biogen, (5) Celgene, (6) Sanofi-Genzyme, (7) Genentech, (8) GlaxoSmithKline, (9) Merck-Serono, (10) Novartis, (11) Roche and (12) Teva.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. (1) Sanofi-Genzyme, (2) Takeda, (3) Merck

    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

  12. Sharmilee Gnananpavan, PhD,
    13. Scientific Advisory Boards:

    1. Dr Gnanapavan has received compensation for participation on scientific advisory boards for Genzyme, Novartis, Biogen and Merck.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. (1)Travel and speaker honoraria from Teva, Genzyme and Novartis.

    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. Reasearch grant from Merck in 2019.

    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

  13. David Baker, PhD,
    14. Scientific Advisory Boards:

    1. (1) Lundbeck (2) Merck

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. (1) Merck (2) Novartis (3) Roche

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Canbex Therapeutics (2) Japan Tobacco

    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. The laboratory received funds for research from a academic entities unrelated to the subject of the manuscript

    Research Support, Foundations and Societies:

    1. The laboratory received funds for research from Charities (Multiple sclerosis Society, Innovative UK/Technology Strategy Board, Diabetes UK, National Multiple Sclerosis Society), Fight for Sight for studies unrelated to the subject of the manuscript

    Stock/Stock Options/Board of Directors Compensation:

    1. I have recieved stock options from a commercial entity (Canbex Therapeutics) in the past to years or studies unrelated to the subject of the manuscript.

    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. I provided consultancy to legal company acting on behalf of Teva, which was unrelated to the subject of the manuscript.

  14. Emma C. Tallantyre, PhD* and
    15. Scientific Advisory Boards:

    1. I have served on scientific advisory boards for Biogen, Roche and Novartis

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. I have received travel expenses to attend scientific conference from Merck, Biogen and Roche.

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. (1) Novartis

    Speakers' Bureaus:

    1. I have received speaker fees from Takeda.

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. I work on research projects funded by Novartis and Genzyme.

    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

  15. Angray S. Kang, PhD*
    16. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. In one aspect, the invention provides a single polypeptide comprising a nanoluciferase domain that possesses a N-terminus and a C-terminus, a first antibody domain linked to the N-terminus by a covalent linker, and a second antibody domain linked to the C-terminus by a second covalent linker. The GloBody used in the ADA assay has been trademarked and a patent for the technology has been filed.

    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. National Institute for Health Research i4i Connect Project NIHR200325 1 yr. Dates Feb 1st 2019 - 31st of January 2020. Role Collaborator

    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 Blizard Institute (G.S., M.J., G.P., L.A., G.R.L., V.V., K.S., G.G., S.G., D.B., A.S.K.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Division of Psychological Medicine and Clinical Neurosciences (J.M.M., S.L., N.P.R., E.C.T.), Cardiff University School of Medicine, United Kingdom; Department of Biological Sciences (L.A.), National University of Medical Sciences, Rawalpindi, Pakistan; Centre for Oral Immunobiology and Regenerative Medicine (G.R.L., A.S.K.), Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London; Clinical Board:Medicine (Neuroscience) (V.V., K.S., G.G., S.G.), The Royal London Hospital, Barts Health NHS Trust; and Welsh Neuroscience Research Tissue Bank (S.L., N.P.R.), Cardiff University, United Kingdom.
  1. Correspondence
    Dr. Kang a.s.kang{at}qmul.ac.uk
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