Evidence map›Paper›PMID 27078105›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Dimethyl fumarate treatment induces adaptive and innate immune modulation independent of Nrf2.

Ulf Schulze-Topphoff, Michel Varrin-Doyer, Kara Pekarek, Collin M Spencer, Aparna Shetty, Sharon A Sagan, Bruce A C Cree, Raymond A Sobel, Brian T Wipke, Lawrence Steinman and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed, 1 pooled it
19.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

162 citing papers in PubMed, 1 synthesis or guideline pooled it, 293 citations in OpenAlex.

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  17. Inflammasomes in neurodegenerative diseases.Translational neurodegeneration · 2024
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102 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 1 country.

Ulf Schulze-TopphoffDepartment of Neurology, University of California, San Francisco, CA 94143; Program in Immunology, University of California, San Francisco, CA 94143;
Michel Varrin-DoyerDepartment of Neurology, University of California, San Francisco, CA 94143; Program in Immunology, University of California, San Francisco, CA 94143;
Kara PekarekDepartment of Neurology, University of California, San Francisco, CA 94143; Program in Immunology, University of California, San Francisco, CA 94143;
Collin M SpencerDepartment of Neurology, University of California, San Francisco, CA 94143; Program in Immunology, University of California, San Francisco, CA 94143;
Aparna ShettyDepartment of Neurology, University of California, San Francisco, CA 94143; Program in Immunology, University of California, San Francisco, CA 94143;
Sharon A SaganDepartment of Neurology, University of California, San Francisco, CA 94143; Program in Immunology, University of California, San Francisco, CA 94143;
Bruce A C CreeDepartment of Neurology, University of California, San Francisco, CA 94143;
Raymond A SobelDepartment of Pathology, Stanford University, Stanford, CA 94305;
Brian T WipkeBiogen, Inc., Cambridge, MA 02142;
Lawrence SteinmanDepartment of Neurology, Stanford University, Stanford, CA 94305 zamvil@ucsf.neuroimmunol.org steinman@stanford.edu.
Robert H ScannevinBiogen, Inc., Cambridge, MA 02142;
Scott S ZamvilDepartment of Neurology, University of California, San Francisco, CA 94143; Program in Immunology, University of California, San Francisco, CA 94143; zamvil@ucsf.neuroimmunol.org steinman@stanford.edu.
University of California, San Francisco · USBiogen (United States) · USStanford University · US

Funding

B cells in CNS autoimmunityR01AI073737 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZAMVIL, SCOTT S · 2009 to 2013
$1.9M
Regulatory monocytes in CNS autoimmune diseaseR01NS063008 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ZAMVIL, SCOTT S · 2009 to 2013
$1.3M
NIAID NIH HHS R01 AI073737NINDS NIH HHS R01 NS063008
6 · The paper itself

Abstract

Dimethyl fumarate (DMF) (BG-12, Tecfidera) is a fumaric acid ester (FAE) that was advanced as a multiple sclerosis (MS) therapy largely for potential neuroprotection as it was recognized that FAEs are capable of activating the antioxidative transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, DMF treatment in randomized controlled MS trials was associated with marked reductions in relapse rate and development of active brain MRI lesions, measures considered to reflect CNS inflammation. Here, we investigated the antiinflammatory contribution of Nrf2 in DMF treatment of the MS model, experimental autoimmune encephalomyelitis (EAE). C57BL/6 wild-type (WT) and Nrf2-deficient (Nrf2(-/-)) mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 (p35-55) for EAE induction and treated with oral DMF or vehicle daily. DMF protected WT and Nrf2(-/-) mice equally well from development of clinical and histologic EAE. The beneficial effect of DMF treatment in Nrf2(-/-) and WT mice was accompanied by reduced frequencies of IFN-γ and IL-17-producing CD4(+) cells and induction of antiinflammatory M2 (type II) monocytes. DMF also modulated B-cell MHC II expression and reduced the incidence of clinical disease in a B-cell-dependent model of spontaneous CNS autoimmunity. Our observations that oral DMF treatment promoted immune modulation and provided equal clinical benefit in acute EAE in Nrf2(-/-) and WT mice, suggest that the antiinflammatory activity of DMF in treatment of MS patients may occur through alternative pathways, independent of Nrf2.

Indexed as

Adaptive ImmunityAdministration, OralAnimalsCells, CulturedDimethyl FumarateDose-Response Relationship, DrugFemaleImmunity, InnateImmunologic FactorsImmunomodulationImmunosuppressive AgentsMaleMiceMice, Inbred C57BLNF-E2-Related Factor 2SpleenDimethyl FumarateImmunologic FactorsImmunosuppressive AgentsNfe2l2 protein, mouseNF-E2-Related Factor 2dimethyl fumarateEAEM2 monocytesmultiple sclerosisNrf2

Identifiers

PMID27078105
PMCPMC4855599
OpenAlexW2336862132

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.