M Muñoz-Culla1, H Irizar1, T Castillo-Triviño2, M Sáenz-Cuesta1, L Sepúlveda1, I Lopetegi3, A López de Munain4, J Olascoaga2, S E Baranzini5, D Otaegui6. 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.
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.
Authors: Keren Regev; Brian C Healy; Fariha Khalid; Anu Paul; Renxin Chu; Shahamat Tauhid; Subhash Tummala; Camilo Diaz-Cruz; Radhika Raheja; Maria A Mazzola; Felipe von Glehn; Pia Kivisakk; Sheena L Dupuy; Gloria Kim; Tanuja Chitnis; Howard L Weiner; Roopali Gandhi; Rohit Bakshi Journal: JAMA Neurol Date: 2017-03-01 Impact factor: 18.302
Authors: María I Dominguez-Mozo; Ignacio Casanova; Laura De Torres; Yolanda Aladro-Benito; Silvia Perez-Perez; Angel Garcia-Martínez; Patricia Gomez; Sara Abellan; Esther De Antonio; Carlos Lopez-De-Silanes; Roberto Alvarez-Lafuente Journal: Front Immunol Date: 2022-06-14 Impact factor: 8.786
Authors: Maria Meira; Claudia Sievers; Francine Hoffmann; Aiden Haghikia; Maria Rasenack; Bernhard F Décard; Jens Kuhle; Tobias Derfuss; Ludwig Kappos; Raija L P Lindberg Journal: Neurol Neuroimmunol Neuroinflamm Date: 2016-03-31