Quinacrine promotes replication and conformational mutation of chronic wasting disease prions

• DOI: 10.1073/pnas.1322377111
• Publication Date: 2014-04-08T04:10:32Z
• Authors: Jifeng Bian; Hae-Eun Kang; Glenn C. Telling
• Keywords: 0301 basic medicine; PrPSc Proteins; Cell Survival; Prions; Protein Conformation; Deer; Cell Line; Prion Diseases; 3. Good health; Mice; 03 medical and health sciences; Quinacrine; Mutation; Animals; Humans; Wasting Disease, Chronic

Significance

Searching for drugs to prevent conversion of host-encoded prion protein (PrP C ) to its infectious conformation (PrP Sc ) is a key strategy in the pursuit of therapies for prion disorders: fatal, transmissible epidemic diseases of unpredictable occurrence and uncertain zoonotic potential. Despite quinacrine’s ability to reduce mouse PrP Sc in cell models, its use to treat patients has been unsuccessful. Here, we show that quinacrine augments PrP Sc and intensifies replication of prions, causing chronic wasting disease of deer, elk, and moose, and that the resulting prions have altered conformational and transmission properties. Our finding, that a drug capable of restraining PrP Sc in one species acts to improve replicative ability and induce mutation in another, forces reexamination of current strategies to combat these diseases.