Infectious Prions Mutate Structurally

Conversion of normal prion protein into a misfolded, infectious form has generally been viewed as a one-to-one process in which each strain of prion protein misfolds into a specific form. But in unexpected findings with implications for drug design, researchers have discovered that misfolded prions can refold and thus evolve structurally. Charles Weissmann and coworkers of Scripps Florida report that prions from infected brain cells change their properties, and by implication their structures, when transferred to cultured cells and then change further when transferred back (Science, DOI: 10.1126/science.1183218). They also found that, in the presence of the prion-inhibiting drug swainsonine, infectious prions evolve into a drug-resistant form. Prion diseases such as mad cow disease and Creutzfeldt-Jakob disease in people are lethal and incurable, so drugs to fight the conditions are being sought. Weissmann and coworkers suggest that in view of the newfound ability of infectious prions to mutate and potentially evade drugs designed against them, it might be best to design drugs that target normal prion protein instead of the shape-shifting infectious forms.