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  • Title: Blood miRNA expression pattern is a possible risk marker for natalizumab-associated progressive multifocal leukoencephalopathy in multiple sclerosis patients.
    Author: Muñoz-Culla M, Irizar H, Castillo-Triviño T, Sáenz-Cuesta M, Sepúlveda L, Lopetegi I, López de Munain A, Olascoaga J, Baranzini SE, Otaegui D.
    Journal: Mult Scler; 2014 Dec; 20(14):1851-9. PubMed ID: 24852919.
    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.
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