Scientists believe that prion diseases — such as scrapie in sheep, 'mad-cow disease' in cattle and Creutzfeldt–Jakob disease in humans — are promoted by the conversion of normal cellular prion protein (PrPC) into the disease-inducing form (PrPSc). A new study in Cell now shows that the two types of prions bind to each other, and that an engineered prion form might help cure disease.

Technical obstacles had previously prevented the demonstration of a physical interaction between PrPC and PrpSc in vivo. But to overcome certain practical impediments, Adriano Aguzzi, from the University Hospital of Zürich, Switzerland, and his colleagues engineered an artificial prion — PrP-Fc2 — that consisted of soluble, dimerized PrPC fused to immunoglobulin Fcγ.

When the soluble dimeric prion protein was expressed in transgenic mice, which were subsequently inoculated with scrapie prion, Aguzzi and colleagues found that PrPSc accumulation, prion replication and onset of disease were significantly delayed.

The researchers could also show — using immunoprecipitation and pull-down asays — that PrP-Fc2 and PrPSc interacted, in vitro and in vivo. “It's the cleanest evidence yet” for the interaction, says prion researcher Michael Scott of the University of California in San Francisco. “It mimics the normal situation.” (Nature Science Update, 4th April 2003).

“PrPFc2 is capable of interfering with the replication of pathological prion and the effect is very robust...”, says Aguzzi (Cell Press Release, 3rd April 2003). This suggests that soluble PrP derivatives might represent a new class of antiprion agents.