Why the study?
Does mefloquine inhibit PrP-res formation in vitro and delay scrapie onset in vivo?
Does mefloquine inhibit PrP-res formation in vitro and delay scrapie onset in vivo?
Mefloquine demonstrates in vitro antiprion activity but lacks in vivo efficacy, highlighting the necessity of in vivo testing for prion disease candidates.
In vitro PrP-res inhibition by mefloquine does not translate to in vivo scrapie delay; leaves open predictive value of cell assays for prion candidates.
In view of the effectiveness of antimalaria drugs inhibiting abnormal protease-resistant prion protein (PrP-res) formation in scrapie agent-infected cells, we tested other antimalarial compounds for similar activity. Mefloquine (MF), a quinoline antimalaria drug, was the most active compound tested against RML and 22L mouse scrapie agent-infected cells, with 50% inhibitory concentrations of approximately 0.5 and approximately 1.2 microM, respectively. However, MF administered to mice did not delay the onset of intraperitoneally inoculated scrapie agent, the result previously observed with quinacrine. While most anti-scrapie agent compounds inhibit PrP-res formation in vitro, many PrP-res inhibitors have no activity in vivo. This underscores the importance of testing promising candidates in vivo.
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Kocisko et al. (2005) studied this question.
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