Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology: Neuroimmunology & Neuroinflammation COVID-19 Article Hub
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
    • UDDA Revision Series
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

User menu

  • My Alerts
  • Log in

Search

  • Advanced search
Neurology Neuroimmunology & Neuroinflammation
Home
A peer-reviewed clinical and translational neurology open access journal
  • My Alerts
  • Log in
Site Logo
  • Home
  • Articles
  • Issues
  • COVID-19 Article Hub
  • Infographics & Video Summaries

Share

March 2022; 9 (2) ArticleOpen Access

Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions

View ORCID ProfileNicole Zinger, Gerald Ponath, View ORCID ProfileElizabeth Sweeney, Thanh D. Nguyen, Chih Hung Lo, Ivan Diaz, View ORCID ProfileAlexey Dimov, Leilei Teng, Lily Zexter, Joseph Comunale, Yi Wang, View ORCID ProfileDavid Pitt, View ORCID ProfileSusan A. Gauthier
First published January 19, 2022, DOI: https://doi.org/10.1212/NXI.0000000000001138
Nicole Zinger
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
BS
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nicole Zinger
  • For correspondence: nicolezinger4@gmail.com
Gerald Ponath
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ponath@tolerogenixx.com
Elizabeth Sweeney
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Elizabeth Sweeney
  • For correspondence: ems4003@med.cornell.edu
Thanh D. Nguyen
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: tdn2001@med.cornell.edu
Chih Hung Lo
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: chihhung.lo@yale.edu
Ivan Diaz
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ild2005@med.cornell.edu
Alexey Dimov
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexey Dimov
  • For correspondence: ald2031@med.cornell.edu
Leilei Teng
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: leilei.teng@greenwichhospital.org
Lily Zexter
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
BA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: lily.zexter@downstate.edu
Joseph Comunale
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: joc2018@med.cornell.edu
Yi Wang
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
PhD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: yiwang@med.cornell.edu
David Pitt
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David Pitt
  • For correspondence: david.pitt@yale.edu
Susan A. Gauthier
From the Department of Neurology (N.Z., L.Z., S.A.G.), Weill Cornell Medicine, New York; Department of Neurology (G.P., C.H.L., D.P.), Yale School of Medicine, New Haven, CT; Department of Population Health Sciences (E.S., I.D.), and Department of Radiology (T.D.N., A.D., J.C., Y.W., S.A.G.), Weil Cornell Medicine, New York; Department of Medicine (L.T.), Yale New Haven Hospital, New Haven, CT; Feil Family Brain and Mind Institute (S.A.G.), Weill Cornell Medicine, New York; and Lee Kong Chian School of Medicine (C.H.L.), Nanyang Technological University, Singapore.
DO, MPH
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Susan A. Gauthier
Full PDF
Citation
Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions
Nicole Zinger, Gerald Ponath, Elizabeth Sweeney, Thanh D. Nguyen, Chih Hung Lo, Ivan Diaz, Alexey Dimov, Leilei Teng, Lily Zexter, Joseph Comunale, Yi Wang, David Pitt, Susan A. Gauthier
Neurol Neuroimmunol Neuroinflamm Mar 2022, 9 (2) e1138; DOI: 10.1212/NXI.0000000000001138

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
1277

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

Abstract

Background and Objectives To determine the effects of dimethyl fumarate (DMF) and glatiramer acetate on iron content in chronic active lesions in patients with multiple sclerosis (MS) and in human microglia in vitro.

Methods This was a retrospective observational study of 34 patients with relapsing-remitting MS and clinically isolated syndrome treated with DMF or glatiramer acetate. Patients had lesions with hyperintense rims on quantitative susceptibility mapping, were treated with DMF or glatiramer acetate (GA), and had a minimum of 2 on-treatment scans. Changes in susceptibility in rim lesions were compared among treatment groups in a linear mixed effects model. In a separate in vitro study, induced pluripotent stem cell–derived human microglia were treated with DMF or GA, and treatment-induced changes in iron content and activation state of microglia were compared.

Results Rim lesions in patients treated with DMF had on average a 2.77-unit reduction in susceptibility per year over rim lesions in patients treated with GA (bootstrapped 95% CI −5.87 to −0.01), holding all other variables constant. Moreover, DMF but not GA reduced inflammatory activation and concomitantly iron content in human microglia in vitro.

Discussion Together, our data indicate that DMF-induced reduction of susceptibility in MS lesions is associated with a decreased activation state in microglial cells. We have demonstrated that a specific disease modifying therapy, DMF, decreases glial activity in chronic active lesions. Susceptibility changes in rim lesions provide an in vivo biomarker for the effect of DMF on microglial activity.

Classification of Evidence This study provided Class III evidence that DMF is superior to GA in the presence of iron as a marker of inflammation as measured by MRI quantitative susceptibility mapping.

Glossary

2D=
2 dimensional;
3D=
3 dimensional;
CIS=
clinically isolated syndrome;
DMF=
dimethyl fumarate;
EDSS=
Expanded Disability Status Scale;
ETL=
echo train length;
FA=
flip angle;
FLAIR=
fluid-attenuated inversion recovery;
GA=
glatiramer acetate;
HBSS=
Hanks Balanced Salt Solution;
IL=
interleukin;
iPSC=
induced pluripotent stem cell;
MMF=
monomethyl fumarate;
MS=
multiple sclerosis;
QSM=
quantitative susceptibility mapping;
RRMS=
relapsing-remitting MS;
SCF=
stem cell factor;
T1w=
T1 weighted;
T2w=
T2 weighted;
TE=
echo time;
TI=
inversion time;
TNF=
tumor necrosis factor;
TR=
repetition time

Footnotes

  • Go to Neurology.org/NN for full disclosures. Funding information is provided at the end of the article.

  • ↵* These authors contributed equally as co–senior authors.

  • The Article Processing Charge was funded by the authors.

  • Class of Evidence: NPub.org/coe

  • Received September 18, 2021.
  • Accepted in final form December 10, 2021.
  • 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.

View Full Text

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Glossary
    • Methods
    • Results
    • Discussion
    • Study Funding
    • Disclosure
    • Acknowledgment
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Differentiating Multiple Sclerosis From AQP4-Neuromyelitis Optica Spectrum Disorder and MOG-Antibody Disease With Imaging

Dr. Ann Yeh and Dr. Daniela Castillo Villagrán

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • All Immunology
  • Multiple sclerosis
  • MRI

Alert Me

  • Alert me when eletters are published
Neurology - Neuroimmunology Neuroinflammation: 10 (6)

Articles

  • Articles
  • Issues
  • Popular Articles

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology: Neuroimmunology & Neuroinflammation
Online ISSN: 2332-7812

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise