isatoribine-anhydrous and Hepatitis-C--Chronic

isatoribine-anhydrous has been researched along with Hepatitis-C--Chronic* in 2 studies

Reviews

1 review(s) available for isatoribine-anhydrous and Hepatitis-C--Chronic

ArticleYear
Masked oral prodrugs of toll-like receptor 7 agonists: a new approach for the treatment of infectious disease.
    Current opinion in investigational drugs (London, England : 2000), 2006, Volume: 7, Issue:8

    Toll-like receptor (TLR)7 is a pattern-recognition receptor that activates the innate immune response. Stimulation of TLR7 induces type I interferons, pro-inflammatory cytokines, the upregulation of co-stimulatory molecules and leads to the development of an adaptive immune response. Small-molecule TLR7 agonists with broad-spectrum antiviral activities in animal models have been identified. Such compounds have been examined clinically for a number of different infectious disease indications, leading to marketing approval of one of these agents, imiquimod, for the topical treatment of external genital and perianal papillomavirus infections. In contrast with topical and intravenous routes of administration, compounds delivered orally have exhibited poor tolerability at desired doses, with substantial adverse events associated with gastrointestinal toxicity. However, dosing with masked oral prodrugs of TLR7 agonists, such as ANA-975, limits the adverse events associated with the activation of responsive gastrointestinal immune tissue. As a consequence, the treatment of systemic diseases, such as chronic hepatitis C, can now be explored with orally administered TLR7 agonists.

    Topics: Administration, Oral; Aminoquinolines; Animals; Guanosine; Hepatitis C, Chronic; Humans; Imiquimod; Prodrugs; Toll-Like Receptor 7

2006

Trials

1 trial(s) available for isatoribine-anhydrous and Hepatitis-C--Chronic

ArticleYear
Isatoribine, an agonist of TLR7, reduces plasma virus concentration in chronic hepatitis C infection.
    Hepatology (Baltimore, Md.), 2005, Volume: 42, Issue:3

    Immune-based therapy is the mainstay treatment for chronic hepatitis C virus (HCV) infection but causes multiple side effects and achieves durable viral clearance in only approximately 50% of patients. Most new investigational anti-HCV compounds are direct-acting antivirals for which durability of response and risk of viral mutations and resistance are not yet known. Therefore, continuing discovery and development of new immune-based treatments is desirable. Toll-like receptors (TLRs) are pathogen recognition receptors that initiate the innate immune response. The responsiveness of HCV or other ongoing chronic systemic infections to treatment with a selective TLR agonist has not been reported. Isatoribine is a selective agonist of TLR7. In a proof-of-concept study, we found that once-daily 7-day treatment with intravenous isatoribine 800 mg caused a significant (P = .001) reduction of plasma HCV RNA (mean, -0.76; range, -2.85 to +0.21 log(10) units) in otherwise untreated patients (n = 12) who were chronically infected with HCV. Viral load reduction occurred in patients infected with genotype 1 as well as non-genotype 1 HCV. The reduction of viral load was correlated with induction of markers of a heightened immune antiviral state, including 2'-, 5'- oligoadenylate synthetase levels in whole blood. This treatment was well tolerated, with a low frequency of mild to moderate adverse events. In conclusion, systemic administration of the selective TLR7 agonist isatoribine resulted in dose-dependent changes in immunologic biomarkers and a statistically significant antiviral effect with relatively few and mild side effects.

    Topics: Antiviral Agents; Dose-Response Relationship, Drug; Gene Expression Regulation; Guanosine; Hepacivirus; Hepatitis C, Chronic; Humans; Membrane Glycoproteins; Receptors, Cell Surface; RNA, Viral; Toll-Like Receptor 7; Toll-Like Receptors; Viral Load

2005