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Published online ahead of print on 12 March 2009 as doi:10.1099/vir.0.009936-0
Journal of General Virology 2009;90:1775.

A more recent version of this article appeared on July 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.009936-0
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Oral Pravastatin prolongs survival time of scrapie-infected mice

Vito Vetrugno1, Michele Angelo Di Bari, Romolo Nonno, Maria Puopolo, Claudia D'Agostino, Maurizio Pocchiari and Umberto Agrimi

ISS

1 E-mail: vito.vetrugno{at}iss.it

Statins are potent inhibitors for HMG-CoA reductase in the cholesterol biosynthesis pathway. They are either lipophilic (e.g. Simvastatin) or hydrophilic (e.g. Pravastatin) compounds, considered mainly for long-term treatment of hyper-cholesterolemic individuals. Beneficial effects of statins are not exclusively related to their lipid-lowering action. They also possess, cholesterol-independent, pleiotropic effects (e.g., antiinflammatory and antioxidant). Recent studies revealed that in scrapie-infected mice, treatment with the lipophilic simvastatin delayed disease symptoms and significantly increased survival. In spite it was reported that pravastatin treatment results in measurable levels in the mouse brain, the anti-prion effect of this compound was still not investigated. Pravastatin, being markedly different from other statins, might offer a wider dose-range of safety, for high-doses and long-term administrations, than have lipophilic statins in the treatment of prion diseases. Therefore, we aimed to test the potential therapeutical action of Pravastatin in a model of murine scrapie. Our study showed that high-dose and long-term pravastatin oral treatment, prolong significantly survival times (194 vs. 177 days; Mann-Whitney Test, p = 0.0001) of 139 A scrapie-infected mice in the absence of any obvious toxicity, suggesting that protective effects of statins may be independent from absolute solvent or water drug solubility.

Received 24 December 2008; accepted 7 March 2009.




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