Miravirsen dosing in chronic hepatitis C patients results in decreased microRNA‐122 levels without affecting other microRNAs in plasma

• DOI: 10.1111/apt.13432
• Publication Date: 2015-10-27T02:03:31Z
• Authors: M. H. van der Ree; A. J. van der Meer; A. C. van Nuenen; J. de Bruijne; S. Ottosen; H. L. Janssen; N. A. Kootstra; H. W. Reesink
• Keywords: Adult; Male; 0301 basic medicine; EMC MM-04-20-02-A; Dose-Response Relationship, Drug; Oligonucleotides; Hepatitis C, Chronic; Middle Aged; Real-Time Polymerase Chain Reaction; 3. Good health; MicroRNAs; 03 medical and health sciences; SDG 3 - Good Health and Well-being; Double-Blind Method; Humans; Female; Aged

MicroRNA-122 (miR-122) is an important host factor for hepatitis C virus replication. Administration of miravirsen, anti-miR-122 oligonucleotide, resulted in a dose dependent and prolonged decrease HCV RNA levels chronic patients.To assess the plasma level various miRNAs patients dosed with miravirsen.We included 16 36 who received five injections either 3 mg/kg (n = 4), 5 7 4) miravirsen or placebo over 4-week period double-blind, randomised phase 2a study. Plasma 179 were determined by qPCR compared between placebo.Median miR-122 at baseline receiving was 3.9 × 10(3) to 1.3 10(4) copies/4 μL placebo-dosed (P 0.68). At week 1, 4, 6 10/12, had respectively median 72-fold, 174-fold, 1109-fold 552-fold lower expression than 0.001, as placebo). 4 dosing, miRNA-profiling demonstrated significant miR-210 miR-532-5p (3.0 4.7-fold respectively). However, subsequent longitudinal analysis showed no differences throughout study period.We substantial miravirsen. other not significantly affected antagonising miR-122.