NR AXXP
AU Terry,L.A.; Edwards,J.; Griffin,J.; Jackman,R.; Cashman,N.R.
TI Prion Protein Anti-Tyr-Try-Arg Antibodies Improve Survival in a Mouse Model of BSE
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.120
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Currently there are no therapeutic procedures for the fatal neurodegenerative prion disorders. Antibodies against the normal cellular prion protein (PrPc) can reduce conversion to the abnormal isoform (PrPsc) in both in vitro and in vivo models of the disease. Previously we demonstrated that antibodies directed to a prion protein tyrosine-tyrosine-arginine (YYR) repeat motif selectively recognise PrPsc (Paramithiotis et al., 2003). We investigated the ability of anti-YYR antibodies to specifically neutralise infectivity in a murine model of BSE. At limiting infectivity titres pre-treatment of 301v brain homogenates with purified IgM and IgG anti-YYR antibodies increases the survival rate of VM mice following intracranial inoculation. Histopathological investigation demonstrated a reduction in the presence of vacuoles in the brains of these mice compared with those treated with control antibodies. Infectivity titres are decreased approximately 10 fold and the effects of neutralisation are not dependent on antibody class. Thus, differentially exposed prion protein YYR epitopes provide a putative target for selective binding of therapeutic antibodies during disease whilst potentially leaving the PrPc molecule still functional. These results are the first step in demonstrating the use of anti-YYR specific reagents in an immunotherapeutic model for prion diseases.
Paramithiotis et al., Nat Med 2003 9:893-899
AD L. Terry, J. Edwards, R. Jackman, Veterinary Laboratories Agency, Molecular Pathogenesis and Genetics, UK; J. Griffin, University of Toronto, Canada; N. Cashman, University of British Columbia, Brain Research Centre, Canada
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren: L.A. Terry, J. Griffin, J. Edwards, S. Simonini, R. Sallis, R. Lockey, J. Spiropoulos, R. Jackman und N.R. Cashman)