Treating hepatitis C by blocking a cellular microRNA

Miravirsen is a drug that binds to and blocks the function of a cellular microRNA called miR-122 that is required for the replication of hepatitis C virus (HCV). Treatment of chimpanzees chronically infected with HCV with this drug leads to suppression of viral replication. The results of a phase 2b human clinical trial in HCV infected humans indicate that Miravirsen reduces levels of viral RNA without evidence for viral resistance. I asked virologist Stan Lemon (who appeared recently on TWiV 235) his opinion of these findings. Are you surprised that the antiviral effect of Miravirsen is long lasting? The Janssen study published in NEJM basically recapitulated what Lanford had observed in HCV-infected chimps treated with the compound, with a very slow onset of antiviral effect, and then a very slow rebound as well. This probably reflects the pharmacokinetics and very high stability of the locked nucleic acid compound, and the time required to sequester endogenous miR-122 – changes in serum cholesterol also move very slowly. I think this is why the antiviral effect (and cholesterol effect) are long-lasting. Is it surprising that no resistance to Miravirsen was observed? As for the lack of resistance, it doesn’t surprise me much. This was observed in the chimps as well. The virus is really dependent upon miR-122 for its replication, and can’t readily mutate around it – the requirement for miR-122 reflects more than just the stabilizing effect of miR-122 ...
Source: virology blog - Category: Virology Authors: Tags: Basic virology Information cirrhosis HCV hepatitis C virus hepatocellular carcinoma liver microrna mIR-122 miravirsen viral Source Type: blogs

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Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
Conclusion: Our findings show that HNF4A could be a potential target in overcoming FOLFOX chemoresistance in colorectal cancer. PMID: 32462912 [PubMed - as supplied by publisher]
Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
Authors: Shi X, Zhou R, Zheng L, Jiang M Abstract Aim: The clinicopathological and prognostic significance of C-MYC dysregulation (amplification or overexpression) in esophageal squamous cell carcinoma (ESCC) remains controversial. Therefore, we performed this meta-analysis to elucidate this relationship. Materials &methods: Available studies were retrieved from PubMed, Web of Science, EMBASE and the Cochrane Library, and ten studies with a total of 1432 patients were included in this meta-analysis. Results: Pooled results showed that C-MYC dysregulation was significantly associated with poor overall ...
Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
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Source: Future Medicine: Biomarkers in Medicine - Category: Internal Medicine Tags: Biomark Med Source Type: research
The role of MRI-guided biopsy for diagnosis of prostate cancer; comparison between FUSION and "IN-BORE" approaches. Minerva Urol Nefrol. 2020 May 26;: Authors: D'agostino D, Casablanca C, Mineo Bianchi F, Corsi P, Romagnoli D, Giampaoli M, Fiori C, Schiavina R, Brunocilla E, Artibani W, Porreca A Abstract BACKGROUND: The aim of the present study is to evaluate the difference in terms of feasibility and detection rate of two magnetic resonance imaging (MRI) guided biopsy approaches (MRI fusion versus "in-bore" MRI) in a single tertiary centre. METHODS: We retrospectively identifi...
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