Muñoz-Culla, M. 1, 3 , Irizar, H. 1, 3 , Sepúlveda, L. 1 , Sáenz-Cuesta, M. 1, 3 , Osorio-Querejeta, I. 1, 3 , López de Munain, A. 2, 4, 5, 6 , Castillo-Triviño, T. 1, 4 , Olascoaga, J. 1, 3, 4 , Baranzini, S. 7 & Otaegui, D. 1, 3
1 Biodonostia Institute, Neuroscience Area, Multiple Sclerosis Unit
2 Biodonostia Institute, Neuroscience Area
3 Spanish network on Multiple Sclerosis
4 University Hospital of Donostia, Neurology Department
5 Centro de Investigación Biomédica en red Enfermedades Neurodegenerativas (Ciberned)
6 Department of Medicine, University of the Basque Country (UPV-EHU)
7 Neurology department, University of California San Francisco
Multiple sclerosis (MS) is a common inflammatory and degenerative disease causing neurological disability in young adults. Natalizumab was approved in 2006 for the treatment of MS. It is a monoclonal antibody that binds to the ?4 subunit of integrins, expressed in activated T cells and other mononuclear leucocytes, blocking their adhesion to the endothelial cells. Thus, their migration into the central nervous system (CNS), a necessary event to trigger the autoimmune attack that causes the demyelination, is inhibited. Long-term therapy has been associated with a higher risk of developing progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the CNS caused by a reactivation of a latent infection of the JC virus. Although the global risk can be stratified according to three factors, a biomarker to assess the individual risk is lacking.
We measured the expression of 754 microRNAs, small non-coding RNAs that regulate gene expression, in the blood from 19 natalizumab-treated MS patients during therapy period.
We found differential expression of three miRNA after 12-month therapy between two patients who developed PML after more than two-years therapy and those who did not. Remarkably, this difference was observed prior to the onset of PML, which is very valuable when evaluating the individual risk and continuity of the treatment.
Therefore, we suggest three miRNAs as possible biomarkers for the individual PML risk assessment.