The depletion of α and β PrP from complex mixtures

Prion disorders occur when endogenous prion protein (PrP(C)) undergoes a conformational change from a predominantly α-helix-rich structure to an insoluble β-sheet-rich structure (PrP(Sc)). The resulting PrP(Sc) then in some way facilitates the progressive transformation of nearby PrP(C) to PrP(Sc). In time this results in the deposition of insoluble PrP(Sc) aggregates in the brain; aggregate deposition is irreversible and is ultimately fatal. Prion diseases are transmissible orally or through transplantation (including blood transfusion). Current diagnostic methods are limited in that they lack the ability to distinguish qualitatively between PrP(C) and PrP(Sc). PrP has been shown to bind divalent cations including copper and zinc, these cations are toxic and thus of limited use in the removal of PrP from solutions destined for administration to subjects. We have immobilised Fe(3+) to an inert Sepharose resin; this resin was capable of quantitatively removing endogenous and recombinant PrP(C) and recombinant β PrP from complex solutions. The low toxicity of Fe(3+) suggests that the resin described in this report may be of practical use in the depletion of PrP from blood products destined for human use.