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BMC Neurology
Published in: BMC Neurology 1/2015

Open Access 01-12-2015 | Research article

Transcriptional response to interferon beta-1a treatment in patients with secondary progressive multiple sclerosis

Authors: Michael Gurevich, Gadi Miron, Rina Zilkha Falb, David Magalashvili, Mark Dolev, Yael Stern, Anat Achiron

Published in: BMC Neurology | Issue 1/2015

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Abstract

Background

Interferon (IFN) beta-1a is an approved treatment for relapsing remitting multiple sclerosis (RRMS) and has been examined for use in secondary progressive multiple sclerosis (SPMS). However, no information regarding blood transcriptional changes induced by IFN treatment in SPMS patients is available. Our aim was to identify a subgroup of SPMS patients presenting a gene expression signature similar to that of RRMS patients who are clinical responders to IFN treatment.

Methods

SPMS patients (n = 50, 20 IFN treated and 30 untreated) were classified using unsupervised hierarchical clustering according to IFN inducible gene expression profile identified in RRMS clinical responders to treatment. IFN inducible gene expression profile was determined by finding differentially expressed genes (DEGs) between IFN treated (n = 10) and untreated (n = 25) RRMS patients. Validation was performed on an additional independent group of 27 SPMS IFN treated patients by qRT-PCR.

Results

One hundred and four DEGs, enriched by IFN signaling pathway (p = 7.4E-08), were identified in IFN treated RRMS patients. Classification of SPMS patients based on these DEGs yielded two patient groups: (1) IFN transcriptional responders (n = 12, 60 % of SPMS treated patients) showing gene-expression profile similar to IFN treated RRMS patients; (2) IFN transcriptional non-responders (n = 8) showing expression profile similar to untreated patients. IFN transcriptional responders were characterized by a more active disease, as defined by higher EDSS progression and annual relapse rate.

Conclusion

Within the IFN treated SPMS population, 60 % of patients have a transcriptional response to IFN which is similar to that of RRMS patients who are IFN responders to treatment.
Appendix
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Metadata
Title
Transcriptional response to interferon beta-1a treatment in patients with secondary progressive multiple sclerosis
Authors
Michael Gurevich
Gadi Miron
Rina Zilkha Falb
David Magalashvili
Mark Dolev
Yael Stern
Anat Achiron
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2015
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-015-0495-x

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