Prion diseases such as
Creutzfeldt-Jakob disease in humans,
bovine spongiform encephalopathy in cattle, and
scrapie in sheep are fatal
neurodegenerative diseases for which there is no effective treatment. The pathology of these diseases involves the conversion of a
protease sensitive form of the cellular
prion protein (PrPC) into a
protease resistant infectious form (PrPsc or PrPres). Both in vitro (cell culture and cell free conversion assays) and in vivo (animal) studies have demonstrated the strong dependence of this conversion process on protein sequence homology between the initial
prion inoculum and the host's own cellular
prion protein. The presence of non-homologous (heterologous)
proteins is often inhibitory to this conversion process. We hypothesize that the presence of heterologous
prion proteins from one species might therefore constitute an effective treatment for
prion disease in another species. To test this hypothesis, we infected mice intracerebrally with murine adapted RML-Chandler
scrapie and treated them with heterologous
prion protein (purified bacterially expressed recombinant hamster
prion protein) or vehicle alone. Treated animals demonstrated reduced disease associated pathology, decreased accumulation of
protease-resistant disease-associated
prion protein, with delayed onset of clinical symptoms and motor deficits. This was concomitant with significantly increased survival times relative to mock-treated animals. These results provide proof of principle that recombinant hamster
prion proteins can effectively and safely inhibit
prion disease in mice, and suggest that hamster or other non-human
prion proteins may be a viable treatment for
prion diseases in humans.