Arginine Butyrate

Arginine butyrate and other histone deacetylase inhibitors induce the activity of certain genes. Exposure of EBV-positive tumor cells to butyrate results in robust induction of herpesvirus in immediate-early and early (lytic) genes, including thymidine kinase (TK), and a modest induction of lytic replication. There is now extensive experience in the administration of arginine butyrate over extended periods of time to adults and children with sickle cell anemia or P-thalassemia to therapeutically reactivate fetal globin expression. In vitro studies demonstrated that induction of EBV-TK activity was possible in EBV-immortal-ized B cells and that these previously ganciclovir-resis-tant cells were then rendered susceptible to antiviral nucleoside analogs. Faller et al. have used arginine butyrate to induce the latent viral TK gene expression and enzyme induction in tumor cells and then treated the patients with ganciclovir: 5 of 10 previously refractory patients experienced a complete clinical response and an additional 2 patients achieved a partial response.56

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