Whole blood miRNAs in relapsing MS patients treated with dimethyl fumarate in the phase 4 TREMEND trial

Maria L Elkjaer; Rikke M Lohse; Mark Burton; Jason P Mendoza; Mads Thomassen; Tobias Sejbaek; Zsolt Illes

doi:10.1016/j.jneuroim.2023.578145

Whole blood miRNAs in relapsing MS patients treated with dimethyl fumarate in the phase 4 TREMEND trial

J Neuroimmunol. 2023 Aug 15:381:578145. doi: 10.1016/j.jneuroim.2023.578145. Epub 2023 Jun 26.

Authors

Maria L Elkjaer¹, Rikke M Lohse², Mark Burton³, Jason P Mendoza⁴, Mads Thomassen⁵, Tobias Sejbaek⁶, Zsolt Illes⁷

Affiliations

¹ Department of Neurology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, BRIDGE, University of Southern Denmark, Odense, Denmark; Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. Electronic address: maria.louise.elkjaer@rsyd.dk.
² Department of Neurology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, BRIDGE, University of Southern Denmark, Odense, Denmark; Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
³ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Clinical Genome Center, University of Southern Denmark & Region of Southern Denmark, Odense, Denmark; Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁴ Biogen, Cambridge, MA, USA.
⁵ Department of Clinical Research, BRIDGE, University of Southern Denmark, Odense, Denmark; Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Clinical Genome Center, University of Southern Denmark & Region of Southern Denmark, Odense, Denmark; Human Genetics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁶ Department of Neurology, Hospital of Southwest Jutland, Esbjerg, Denmark.
⁷ Department of Neurology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, BRIDGE, University of Southern Denmark, Odense, Denmark; Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. Electronic address: zsolt.illes@rsyd.dk.

PMID: 37393851
DOI: 10.1016/j.jneuroim.2023.578145

Abstract

We investigated the impact of dimethyl fumarate (DMF), an oral therapy for relapsing multiple sclerosis (MS), on blood microRNA (miRNA) signatures and neurofilament light (NFL) levels. DMF normalized miR-660-5p and modulated various miRNAs associated with the NF-kB pathway. These alterations reached a peak 4-7 months after treatment. Notably, particular miRNAs correlated with high or low NFL levels, implying their potential role as markers of treatment efficacy. Our findings broaden the understanding of DMF's immunomodulatory effects and may aid in predicting treatment responses.

Keywords: Dimethyl-fumarate (DMF); Multiple sclerosis; NF-kB; Neurofilament light chain (NFL); miRNA.

Publication types

Clinical Trial, Phase IV
Research Support, Non-U.S. Gov't

MeSH terms

Dimethyl Fumarate / therapeutic use
Humans
Immunosuppressive Agents / adverse effects
MicroRNAs*
Multiple Sclerosis* / chemically induced
Multiple Sclerosis, Relapsing-Remitting* / chemically induced
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Recurrence

Substances

Dimethyl Fumarate
Immunosuppressive Agents
MicroRNAs
MIRN660 microRNA, human