MicroRNA could affect the action of Tysabri

Meira M, Sievers C, Hoffmann F, Derfuss T, Kuhle J, Kappos L, Lindberg RL.MiR-126: a novel route for natalizumab action? Mult Scler. 2014 Mar . [Epub ahead of print]

BACKGROUND:MicroRNAs (miRNAs) have emerged as a family of post-transcriptional regulators of gene expression that mediate diverse aspects of immunity. MiRNA dysregulation has been found in multiple sclerosis (MS), reflecting the growing need to identify disease-specific miRNA expression signatures. Our previous low-density array studies reveal differential miR-126 expression in the CD4+T cells of untreated relapsing-remitting MS (RRMS) patients. Here, we investigated miR-126 expression in natalizumab-treated patients.
METHODS:We isolated CD4+ T cells from untreated (n = 12) and natalizumab-treated MS patients (n = 24), and from healthy volunteers (n = 12). We analyzed the expression of miRNAs and potential targets by real time reverse transcription polymerase chain reaction (RT-PCR). We assessed specific inhibition of miR-126, in vitro.
RESULTS: MiR-126 was down-regulated in cells of patients under natalizumab treatment and up-regulated during relapse, supporting a regulatory role in MS immunopathogenesis. MiR-126 expression correlated with the expression of POU2AF1, a regulator of Spi-B that binds to the promoter/enhancer sequences of JC virus (JCV), the pathogen of progressive multifocal leukoencephalopathy (PML), a rare complication of natalizumab treatment. The same trend was found for Spi-B. Strong up-regulation of both genes appeared to be treatment duration-dependent. Specific inhibition experiments supported the link between the expression of miR-126 and POU2AF1/Spi-B.
CONCLUSIONS: Our findings provided deeper insight into the mode of action of natalizumab, with possible implications for understanding both the effects of natalizumab on MS activity and its specific adverse event profile.

MicroRNA are epigenetic factors that can control the level of gene expression and this study it is suggested that one of the many hundred microRNA is affected by Tysabri and so could this affect blood brain barrier activty. Well the answer is certainly. microRNA can affect blood brain barrier function and microRNA other than MiR-126 that can do this.

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