A chemical that combats pathogenic prion proteins in infected mouse cells worsens the problem in cells from other species. The finding could explain why the drug, quinacrine, has been ineffective in many clinical trials.

Prion infections turn healthy proteins into abnormally folded forms, which cause fatal neurodegenerative diseases in humans and other animals. Quinacrine reduces this misfolding in mouse cells, but Glenn Telling and his colleagues at Colorado State University in Fort Collins discovered that the drug has the opposite effect in deer, elk and moose cells, causing the proteins to misfold even more. The researchers think that small differences in prion protein sequences between species could be to blame.

Drug developers will need to rethink how they screen molecules for antiprion activity, the authors say.

Proc. Natl Acad. Sci. USA http://doi.org/r9d (2014)