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January 2020; 7 (1) ArticleOpen Access

SHP2 inhibitor protects AChRs from effects of myasthenia gravis MuSK antibody

Saif Huda, Michelangelo Cao, Anna De Rosa, Mark Woodhall, Pedro M. Rodriguez Cruz, Judith Cossins, Michelangelo Maestri, Roberta Ricciardi, Amelia Evoli, David Beeson, Angela Vincent
First published December 12, 2019, DOI: https://doi.org/10.1212/NXI.0000000000000645
Saif Huda
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Michelangelo Cao
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Anna De Rosa
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Mark Woodhall
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Pedro M. Rodriguez Cruz
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Judith Cossins
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Michelangelo Maestri
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Roberta Ricciardi
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Amelia Evoli
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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David Beeson
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Angela Vincent
From the Department of Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
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Full PDF
Citation
SHP2 inhibitor protects AChRs from effects of myasthenia gravis MuSK antibody
Saif Huda, Michelangelo Cao, Anna De Rosa, Mark Woodhall, Pedro M. Rodriguez Cruz, Judith Cossins, Michelangelo Maestri, Roberta Ricciardi, Amelia Evoli, David Beeson, Angela Vincent
Neurol Neuroimmunol Neuroinflamm Jan 2020, 7 (1) e645; DOI: 10.1212/NXI.0000000000000645

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Article Information

vol. 7 no. 1 e645
DOI: 
https://doi.org/10.1212/NXI.0000000000000645
PubMed: 
31831571

Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received August 15, 2019
  • Accepted in final form October 8, 2019
  • First Published December 12, 2019.

Copyright & Usage: 
Copyright © 2019 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. Saif Huda, MD, DPhil*,
    2. Michelangelo Cao, MD, PhD*,
    3. Anna De Rosa, MD,
    4. Mark Woodhall, PhD,
    5. Pedro M. Rodriguez Cruz, MD, DPhil,
    6. Judith Cossins, DPhil,
    7. Michelangelo Maestri, MD,
    8. Roberta Ricciardi, MD,
    9. Amelia Evoli, MD,
    10. David Beeson, PhD and
    11. Angela Vincent, MD, FRCPath, FRS
  1. Saif Huda, MD, DPhil*,
  2. Scientific Advisory Boards:
    1. NONE

    Gifts:
    1. NONE

    Funding for travel or speaker honoraria:
    1. (1) MS Academy, speaker honoraria

    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. (1) University of Liverpool (2) Walton Centre Foundation Trust

    Research Support, Foundations and Societies:
    1. (1) NMO-UK spectrum charity

    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. Michelangelo Cao, MD, 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

  5. Anna De Rosa, MD,
  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

  7. Mark Woodhall, PhD,
  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

  9. Pedro M. Rodriguez Cruz, MD, DPhil,
  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. 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. Judith Cossins, DPhil,
  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. 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

  13. Michelangelo Maestri, MD,
  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. 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. Roberta Ricciardi, MD,
  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. 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

  17. Amelia Evoli, MD,
  18. Scientific Advisory Boards:
    1. scientific advisory board - Alexion data safety monitoring board - UCB

    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. Scientific award jury member for Grifols

    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

  19. David Beeson, PhD and
  20. 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. Medical Research Council Programme Grant MR/M006824/1

    Research Support, Academic Entities:
    1. NONE

    Research Support, Foundations and Societies:
    1. Muscular Dystrophy Campaign Grant RA 722

    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

  21. Angela Vincent, MD, FRCPath, FRS
  22. Scientific Advisory Boards:
    1. NONE

    Gifts:
    1. NONE

    Funding for travel or speaker honoraria:
    1. Bial Commercial, Portugal travel and speaker honorarium

    Editorial Boards:
    1. Advisory Editorial Board Neurology 2014 - Advisory Editorial Board Annals of Neurology 2018 - Associate Editor for Brain ended 2013

    Patents:
    1. Hold patent with Oxford University for MuSK antibodies and for LGI1/CASPR2 antibodies. Receive a proportion of royalties from these tests.

    Publishing Royalties:
    1. Royalties for Clinical Neuroimmunology (Blackwell Publishing, 2005) and Inflammatory and Autoimmune Disorders of the Nervous System in Children (Mac Keith Press 2010) and for Pittock and Vincent Handbook of Neurology 2017 (Elsevier).

    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. NIHR general support for antibody work finished 2016

    Research Support, Foundations and Societies:
    1. FNRS honorarium for Prize Panel work £2000 2017

    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 Clinical Neurosciences (S.H., M.C., M.W., P.M.R.C., J.C., D.B., A.V.), Weatherall Institute of Molecular Medicine and Nuffield, University of Oxford, UK; Department of Clinical and Experimental Medicine (A.D.R., M.M., R.R.), Neurology Unit, Pisa; and Department of Neuroscience (A.E.), Catholic University, Rome, Italy.
  1. Correspondence
    Dr. Vincent angela.vincent{at}ndcn.ox.ac.uk
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Neurology - Neuroimmunology Neuroinflammation: 9 (4)

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Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

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