title: Potential approaches for heterologous prion protein treatment of prion diseases.
abstract: Prion diseases, or transmissible spongiform encephalopathies (TSEs) are progressive, fatal neurodegenerative diseases with no effective treatment. The pathology of these diseases involves the conversion of a protease sensitive form of the cellular prion protein (PrP(C)) into a protease resistant infectious form (PrP(res)). The efficiency of this conversion is predicated upon a number of factors, most notably a strong homology between cellular PrP(C) and PrP(res). In our recently published study, we infected mice with the RML-Chandler strain of scrapie and treated them with heterologous hamster prion proteins. This treatment was seen to reduce clinical signs of prion disease, to delay the onset of clinical symptoms and to prolong survival. In this current article we discuss potential mechanisms of action of treatment with heterologous prion proteins. We also discuss potential extensions of these studies using a heterologous rabbit PrP-based treatment strategy or a peptide based strategy, and improvement of treatment delivery including a lentiviral-based system.
authors.affiliation: a Veterinary Clinical Sciences Department , University of Minnesota , Saint Paul , MN , USA.
authors.forename: Davis M
authors.initials: DM
authors.lastname: Seelig
authors.affiliation: b Veterinary and Biomedical Sciences Department , University of Minnesota , Saint Paul , MN , USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Goodman
authors.affiliation: b Veterinary and Biomedical Sciences Department , University of Minnesota , Saint Paul , MN , USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Skinner
mesh_terms: D000818:Animals; D006224:Cricetinae; D053208:Kaplan-Meier Estimate; D051379:Mice; D018620:PrPSc Proteins / Q000737:chemistry / Q000627:therapeutic use*; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000627:therapeutic use; D012608:Scrapie / Q000188:drug therapy* / Q000401:mortality
chemical_list: D018620:PrPSc Proteins; D011994:Recombinant Proteins
keywords: PrPC; PrPres; heterologous prion proteins; prion; treatment