Randomised clinical trial: anti-viral activity of ANA773, an oral inducer of endogenous interferons acting via TLR7, in chronic HCV

Bergmann, Jean‐François; Bruijne, Joep de; Hotho, Daphne M.; Knegt, Robert J. de; Boonstra, André; Weegink, Christine J.; Vliet, André A. van; Wetering, J. van de; Fletcher, Simon P.; Bauman, Lisa; Rahimy, Mohamad H.; Appleman, James R.; Freddo, James L.; Janssen, Harry L.A.; Reesink, H. W.

doi:10.1111/j.1365-2036.2011.04745.x

Cited by 55 publications

(41 citation statements)

References 14 publications

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“…The drug was generally well tolerated and most of the reported adverse events symptoms disappeared rapidly during continued dosing, resulting in no dose reductions or discontinuations. Thus, ANA773 is the first oral TLR7 agonist to induce a dose-related antiviral response leading to a significant decrease in serum HCV RNA levels without the concurrent induction of prohibitive systemic side effects [55]. Hence, it is plausible that viral eradication may be enhanced using a strategy that optimally targets the host innate immune system by using an oral selective TLR7 agonist to induce a direct antiviral effect (type I interferon signature) and an indirect effect (enhancing HCV-specific immunity by cross-linking innate and adaptive immune system), resulting in rapid eradication of HCV without a myriad of adverse events.…”

Section: Reviewmentioning

confidence: 99%

Tickling the TLR7 to cure viral hepatitis

et al. 2014

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Chronic hepatitis B and C are the leading causes of liver disease and liver transplantation worldwide. Ability to mount an effective immune response against both HBV and HCV is associated with spontaneous clearance of both infections, while an inability to do so leads to chronicity of both infections. To mount an effective immune response, both innate and adaptive immune responses must work in tandem. Hence, developing protective immunity to hepatitis viruses is an important goal in order to reduce the global burden of these two infections and prevent development of long-term complications. In this regard, the initial interactions between the pathogen and immune system are pivotal in determining the effectiveness of immune response and subsequent elimination of pathogens. Toll-like receptors (TLRs) are important regulators of innate and adaptive immune responses to various pathogens and are often involved in initiating and augmenting effective antiviral immunity. Immune-based therapeutic strategies that specifically induce type I interferon responses are associated with functional cure for both chronic HBV and HCV infections. Precisely, TLR7 stimulation mediates an endogenous type I interferon response, which is critical in development of a broad, effective and protective immunity against hepatitis viruses. This review focuses on anti-viral strategies that involve targeting TLR7 that may lead to development of protective immunity and eradication of hepatitis B.

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Section: Reviewmentioning

confidence: 99%

Tickling the TLR7 to cure viral hepatitis

et al. 2014

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“…In a previous study, oral administration of the TLR7 agonist, SM‐360320 was found to generate potent antitumor immune responses in carcinoembryonic antigen transgenic mice bearing MC38 colon adenocarcinoma cells 33. In addition, oral administration of TLR7 agonists have been tested clinically (using the prodrug TLR7 agonist ANA773) and preclinically for the treatment of hepatitis C virus infection 34, 35. In the present study we compared IT and PO administration of SM‐276001 in the HM‐1 model of metastatic ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Delay in receiving rheumatology care leads to long‐term harm

Bykerk¹,

Emery²

2010

Arthritis & Rheumatism

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In our study the effects of various factors in the reaction of chlorination and copolymerization of fatty acid wastes were investigated and optimum conditions were determined. The first purpose of this study is to investigate the electrochemical chlorination reaction of fatty acid wastes in the electrolysis of HCl, then to obtain composite materials by the products of this reaction, and finally to determine physicomechanical properties, heat resistance, and the effect of chloride to the fire strength of these composite materials. At that time the glycide ester of fatty acid (GEF) was synthesized and used as modificator for the determination of thermal and heat properties of composite materials. And the properties of composite materials that are obtained were compared. Styrene‐fatty acid copolymers (SFC) were also synthesized by interacting wasted product with styrene. Molecular weight of copolymer, number of carboxyl groups in its structure, its adhesion capability and thermal properties were investigated. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

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“…A subsequent oral prodrug of isatoribine, ANA773, showed efficient induction of type I IFN and proved to be safe and well tolerated in preclinical studies. In a double-blind, placebo-controlled study of patients infected chronically with HCV, ANA773 showed a dose-dependent increase in IFN responses and a decrease in serum HCV RNA [147]. Repeated administration of ANA773 to chronic HCV patients resulted in a transient reduction in blood myeloid DC and pDC numbers and increased serum levels of IFN-α and IP-10 only in patients, who showed reduced serum HCV RNA upon drug treatment [148].…”

Section: Tlr7/8mentioning

confidence: 99%

Novel Drugs Targeting Toll-Like Receptors for Antiviral Therapy

et al. 2014

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Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved ‘pathogen-associated molecular patterns’ of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release ‘danger-associated molecular patterns’ that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

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Randomised clinical trial: anti-viral activity of ANA773, an oral inducer of endogenous interferons acting via TLR7, in chronic HCV

Cited by 55 publications

References 14 publications

Tickling the TLR7 to cure viral hepatitis

Tickling the TLR7 to cure viral hepatitis

Delay in receiving rheumatology care leads to long‐term harm

Novel Drugs Targeting Toll-Like Receptors for Antiviral Therapy

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