Pharmacological studies of a new derivative of @entity2379 , XXXX , in @entity19 and hamster scrapie.

@entity2379 @entity19 @entity71201 @entity1579 @entity281 @entity27465 @entity179 @entity11015
@entity1579 ( @entity1579 ) are @entity179 characterized by the presence of a modified, partially proteinase-resistant host protein, @entity27465 , which accumulates in the brains of infected individuals. Recently it has been reported that @entity2379 ( @entity11015 ) treatment of hamsters infected with scrapie strain 263K prolongs the incubation period of the disease, and dissociates in vivo replication of the scrapie agent from @entity27465 accumulation. We report here on data obtained after treatment with @entity11015 and one of its derivatives, @entity71201 , in experimental scrapie of @entity19 and hamster. Treatment was carried out by the intraperitoneal route 6 days per week, at three different dosages initiated at the time of @entity281 . Two regimens were used: during the early time of @entity281 or throughout the experimental @entity281 . Results indicate that @entity71201 was as efficient as @entity11015 in prolonging the incubation time and decreasing @entity27465 accumulation in the hamster scrapie model. A dose-dependent response was observed in @entity19 treated early after experimental @entity281 . At a dose of 2.5 mg/kg, @entity71201 significantly prolonged the incubation period (by 11.9%). In long-term treatment of @entity19 , @entity71201 and @entity11015 markedly reduced @entity27465 levels in the preclinical stage of the disease. These data demonstrate that the effect of @entity11015 is not restricted to one model (hamster-263K). This regimen leads to an inversion of the @entity27465 to proteinase-sensitive protein (PrPSens) ratio, suggesting PrPSens (presumably cellular @entity27465 ) accumulation occurs before its conversion into @entity27465 . As it has been shown that @entity11015 does not modify the infectivity titre, we conclude that the drugs could act by inhibiting either the interaction of the scrapie agent with PrPSens during the early times of @entity281 or the conversion of PrPSens into @entity27465 .
