Simvastatin treatment prolongs the survival of scrapie-infected mice.
Statins, drugs that decrease cholesterol biosynthesis, are known to reduce the formation of the disease-associated isoform of the prion protein (PrP) in neuroblastoma cells in vitro. In this study, we report the effects of simvastatin, a clinically approved statin that penetrates the brain, on mice infected with the ME7 strain of scrapie. The decline in motor functions associated with scrapie infection was delayed in mice receiving (1 mg/kg) simvastatin, a dosage used to treat hypercholesterolemia in humans. Simvastatin treatment also significantly prolonged the survival times of infected mice (193 vs. 183 days). These results indicate that low-dosage simvastatin treatment affects the progression of experimental scrapie, and supports the concept that statin treatment may influence the prion pathogenesis.
Kempster
Sarah
S
Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Hospital, Robinson Way, Cambridge, UK.
Bate
Clive
C
Williams
Alun
A
D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D017096:Prion Diseases / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D019821:Simvastatin / Q000008:administration & dosage*; D015996:Survival Rate
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D019821:Simvastatin