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Mult Scler. 2014 Dec;20(14):1851-9. doi: 10.1177/1352458514534513. Epub 2014 May 22.

Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients.

Author information

1
Biodonostia Health Research Institute, San Sebastián, SpainSpanish network on Multiple Sclerosis.
2
Spanish network on Multiple SclerosisBiodonostia Health Research Institute, San Sebastián, Spain/Hospital Universitario Donostia, San Sebastián, Spain.
3
Biodonostia Health Research Institute, San Sebastián, Spain.
4
Biodonostia Health Research Institute, San Sebastián, Spain/Hospital Universitario Donostia, San Sebastián, Spain/University of the Basque Country (UPV-EHU), San Sebastián, Spain/Centro de Investigación Biomédica en red Enfermedades Neurodegenerativas (CIBERNED).
5
University of California at San Francisco, USA.
6
Biodonostia Health Research Institute, San Sebastián, SpainSpanish network on Multiple Sclerosis david.otaegui@biodonostia.org.

Abstract

BACKGROUND:

Natalizumab has shown its efficacy in reducing multiple sclerosis (MS) relapses and progression of disability; however, it has been associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML). The differential expression of microRNA (miRNA), the small non-coding RNAs that regulate gene expression, in natalizumab-treated patients has been reported and miRNA have also been described as good candidates for disease biomarkers.

OBJECTIVE:

To characterize the effect of natalizumab therapy on the miRNA expression pattern and to search for miRNAs that can predict PML on an individual basis.

METHODS:

The expression of 754 microRNAs was measured in blood samples from 19 relapsing-remitting MS patients at three time points during natalizumab therapy, using TaqMan OpenArray panels. Two patients included in this study developed PML after more than 2 years of therapy.

RESULTS:

We found that the expression level of three miRNAs (let-7c, miR-125a-5p and miR-642) was affected after 6 months of therapy (t6). Furthermore, we observed a differential expression of another three miRNAs (miR-320, miR-320b and miR-629) between the PML and non-PML groups after 12 months of treatment (t12); and a positive correlation was found between therapy time and the expression of miR-320.

CONCLUSIONS:

Natalizumab modified the expression levels of three miRNAs after a 6-month treatment. We suggest miR-320, miR-320b and miR-629 as possible biomarkers for individual PML risk assessment.

KEYWORDS:

Adverse effects; biomarker; miRNA expression; microRNA; multiple sclerosis; natalizumab; progressive multifocal leukoencephaly; risk factors

PMID:
24852919
DOI:
10.1177/1352458514534513
[Indexed for MEDLINE]

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