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

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.