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January 2023; 10 (1) Research ArticleOpen Access

Serum GFAP and NfL Levels Differentiate Subsequent Progression and Disease Activity in Patients With Progressive Multiple Sclerosis

Christian Barro, Brian C. Healy, Yanqing Liu, Shrishti Saxena, Anu Paul, Mariann Polgar-Turcsanyi, Charles R.G. Guttmann, Rohit Bakshi, Harald Kropshofer, Howard L. Weiner, Tanuja Chitnis
First published November 14, 2022, DOI: https://doi.org/10.1212/NXI.0000000000200052
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Article Information

vol. 10 no. 1 e200052
DOI: 
https://doi.org/10.1212/NXI.0000000000200052
PubMed: 
36376097
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Online ISSN: 
2332-7812
History: 
  • Received March 14, 2022
  • Accepted in final form September 6, 2022
  • First Published November 14, 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-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. Christian Barro,
    2. Brian C. Healy, PhD,
    3. Yanqing Liu, MSc,
    4. Shrishti Saxena, MSc,
    5. Anu Paul, MSc,
    6. Mariann Polgar-Turcsanyi, MSc,
    7. Charles R.G. Guttmann, MD,
    8. Rohit Bakshi, MD,
    9. Harald Kropshofer, PhD,
    10. Howard L. Weiner, MD and
    11. Tanuja Chitnis, MD
  1. Christian Barro,
    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. Brian C. Healy, PhD,
    3. Scientific Advisory Boards:

    1. None

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. None

    Editorial Boards:

    1. Statistical Methods in Medical Research 2008

    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) Analysis Group, (2) Celgene (Bristol-Myers Squibb), (3) <br>Verily Life Sciences, (4) Merck-Serono, (5) Novartis, and <br>(6) 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

  3. Yanqing Liu, MSc,
    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. Shrishti Saxena, MSc,
    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. Anu Paul, MSc,
    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. Currently employed at Moderna Tx since May 2022 as a Senior

    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. Mariann Polgar-Turcsanyi, 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. Charles R.G. Guttmann, MD,
    8. Scientific Advisory Boards:

    1. 1. Sintetica (Scientific Advisory Board)

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. 1. EDMUS Foundation, Observatoir Francais de la Sclerose<br>en Plaque Project, Lyon, France, Travel<br>2. University of Bordeaux; travel<br>3. Universitad de Los Andes, Bogota, Colombia, Travel<br>4. MEDAMI Conference, Italy, Travel<br>5. Ecole Polytechnique Federale Lausanne (EPFL), Lausanne,<br>Switzerland, Travel<br>6. University Hospital Strasbourg, Strasbourg, France, Travel<br>7. University Hospital Bari, Bari, Italy, Travel<br>8. Charit&#x00E9; University Hospital, Berlin, Germany, Travel<br>9. Institut universitaire de g&#x00E9;riatrie de Montr&#x00E9;al,<br>Canada, Travel<br>10. Guthy Jackson Charitable Foundation, Los Angeles, CA,<br>U.S.A. Travel<br>11. Sapienza University of Rome, Italy, Travel<br>12. Hungarian Medical Association of America, U.S.A., Travel<br>13. Institut National Sciences Appliqu&#x00E9;es, Lyon, France,<br>Travel<br>14. McGill University, Montreal, Canada, Travel<br>15. University Hospital, Odense, Denmark, Travel<br>16. Mediri, Germany, Travel<br>17. Max Planck Institut, Leipzig, Germany, Travel<br>18. University Hospital Graz, Austria, Travel<br>19. Centro Ettore Majorana, Erice, Italy<br>20. Tel Aviv University, Israel, Travel<br>21. American University Beirut, Lebanon, Travel<br>22. ARSEP, Paris, France, Travel

    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. 1. Sapienza - University of Rome, Adjunct Professor<br>2. Institut National Sciences Appliqu&#x00E9;es, Lyon, France,<br>Visiting Professor<br>3. University of Bordeaux, Visiting Professor

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. 1. National Multiple Sclerosis Society, RG 4354-A-2,<br>Co-Investigator, 2011-2014<br>2. NIH/University of CT Health Center, R01AG022092, Site<br>Principal Investigator, 2011-2017<br>3. National Multiple Sclerosis Society, RG 4256A4-2,<br>Co-Investigator, 2010-2013<br>4. ITN/NIH, N01AI15416, Co-Investigator, 2010-2014<br>5. NIH, U01AI063623, Co-Investigator, 2009-2014<br>6. NIH/NCRR, UL1 RR025758, Co-Investigator, 2008-2013<br>7. National Multiple Sclerosis Society, RR 2005-A-13,<br>Co-Investigator, 2010-2013<br>8. NIH, P41RR013218 Supplement, Co-Investigator, 2009-2011<br>9. Office of Naval Research, N00014-15-1-2408,<br>Co-Investigator, 2015-2017<br>10. NIH, 3R01MH112748-03S1, Co-Investigator, 2020-2021

    Research Support, Academic Entities:

    1. 1. University of Bordeaux

    Research Support, Foundations and Societies:

    1. 1. National Multiple Sclerosis Society, RG 4256A4-2,<br>Principal Investigator, 2015-2018<br>2. International Progressive Multiple Sclerosis<br>Alliance/Montreal Neurological Institute and Hospital,Co-Investigator, 2017-2022<br>3. National Multiple Sclerosis Society, PP-1905-34011,<br>Principal Investigator, 2019-2020<br>4. National Multiple Sclerosis Society,PP-2001-35512, Co-Investigator, 2020-2021<br>5. BrightFocus Foundation, Co-Investigator, 2020-2023<br>6. Foundation of the University of Bordeaux

    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. 1. Novartis, >10 years<br>2. Roche, >10 years<br>3. GSK, >10 years<br>4. Nestle, >10 years<br>5. Alnylam, 2010-to date<br>6. ISIS, 2012-2013<br>7. Apple, 2009-present<br>8. Arrowhead, 2013-present<br>9. Cocrystal Pharma Inc., 2014-present<br>10. Protalix Biotherapeutics Inc., 2013-present<br>11. Sangamo Therapeutics Inc., 2014-present<br>12. Alcon, 2019-present

    Legal Proceedings:

    1. NONE

  8. Rohit Bakshi, MD,
    9. Scientific Advisory Boards:

    1. Dr. Bakshi serves as Editor-in-Chief of (1) the Journal of<br>Neuroimaging

    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. Dr. Bakshi has received consulting fees from (1) EMD Serono and (2) Bristol-Myers Sqibb.

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Dr. Bakshi has received research support from (1) EMD<br>Serono and (2) Novartis, and (3) Bristol-Myers Squibb.

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Dr. Bakshi has received research support from the (1)<br>Department of Defense (W81XWH-18-1-0648 and W81XWH1910836), (2) National Multiple Sclerosis Society (RR 2005-A-13 and RG-1707-28586), (3) Water Cove foundation, (4) Race to Erase MS, and (4) NIH (1 R03 EB30831-01).

    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. Harald Kropshofer, 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. 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. Howard L. Weiner, MD and
    11. Scientific Advisory Boards:

    1. I-Mab Biopharma<br><br><br><br>Weston Foundation

    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. Tiziana Life Sciences<br><br><br><br>vTv Therapeutics

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Genzyme Corp<br><br><br><br>Genentech, Inc. <br><br><br><br>Verily Life Sciences LLC

    Research Support, Government Entities:

    1. NIH<br><br><br><br> R01 NS115951 - PI - 01/15/21 &#x0096; 12/31/25<br><br><br><br> RF1 AG065270 - PI - 09/30/20 &#x0096; 08/31/24<br><br><br><br> R21 AG063187 - PI - 03/01/20 &#x0096; 02/28/22<br><br><br><br> R01 EY027921 - PI - 09/01/17 &#x0096; 12/31/20

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. National Multiple Sclerosis Society<br><br><br><br>Cure Alzheimer&#x0092;s Fund<br><br><br><br>Foundation for Neurologic Diseases<br>Stock/Stock Options/Board of Directors Compensation: <br>vTv Therapeutics

    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. Tanuja Chitnis, MD
    12. Scientific Advisory Boards:

    1. Dr. Chitnis has served on clinical trial advisory boards <br>for Novartis Pharmaceuticals, Roche-Genentech and Sanofi-Genzyme.

    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. Dr. Chitnis has served as a one-time consultant for Biogen, Genentech-Roche, <br>Novartis and Sanofi-Genzyme, Tiziana Life Sciences

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Dr. Chitnis receives research support from (1) Sanofi-Genzyme (2) Novartis in <br>the form of Independent Investigator Awards.

    Research Support, Government Entities:

    1. NIH, Department of Defense

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Dr. Chitnis has received research support from the National<br>Multiple Sclerosis Society, the Peabody Foundation, the <br>Sumaira Foundation and the Guthy-Jackson Charitable Foundation.

    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 Harvard Medical School (C.B., B.C.H., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.); Ann Romney Center for Neurologic Diseases (C.B., B.C.H., Y.L., S.S., A.P., M.P.-T., C.R.G.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital; Brigham Multiple Sclerosis Center (R.B., H.L.W., T.C.), Department of Neurology, Brigham and Women's Hospital; Center for Neurological Imaging (C.R.G.G.), Department of Radiology, Brigham and Women's Hospital; Biostatistics Center (B.C.H.), Massachusetts General Hospital, Boston, MA; and Novartis Pharma AG (H.K.), Basel, Switzerland.
  1. Correspondence
    Dr. Chitnis tchitnis{at}rics.bwh.harvard.edu
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