NR AXWW
AU Song,C.H.; Furuoka,H.; Suzuki,A.; Ogino,M.; Horiuchi,M.
TI Effect of Intraventricular Infusion of Anti-PrP mAbs on the Disease Progression in Scrapie-Infected Mice
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.167
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Anti-PrP monoclonal antibodies (mAbs) have been shown to inhibit PrPsc formation in cells persistently infected with prion, and passive immunization could protect the animals from prion infection through peripheral challenge when anti-PrP mAbs were administered in the early stage of infection. These results suggest that the mAbs are candidate for a treatment of prion diseases, however, the effect of mAbs on disease progression at middle-late stage of the disease remains unclear. Therefore, to evaluate the therapeutic effect of anit-PrP mAbs, we carried out intraventricular infusion of the mAbs before and just after the onset of the disease. Scrapie Obihiro and Chandler strains were used in this study. Anti-PrP mAbs were infused into lateral ventricule using Alzet mini-osmotic pump. For the analysis of the effect on PrPsc accumulation and neurodegeneration, infusions (for 4-week) were started at 120 days post infection (dpi) and mice were sacrificed at 150 dpi. For evaluation of the effect on the prolongation, infusions (for 2-week) were started at 60, 90, (before onset) and 120 dpi (just after onset). After the 4-week infusion started at 120 dpi, anti-PrP mAbs reduced PrPsc level to 70-80% of mice treated with negative control mAb. This reduction was due to the deceleration of PrPsc accumulation by anti-PrP mAbs. Spongiform changes and astrocytosis in hippocampus and thalamus of mice treated with anti-PrP mAbs appeared milder than those of mice treated with negative control mAb. The anti-PrP mAb prolonged the incubation period of mice infected with Obihiro strain when infusion was started at 60 dpi, while prolongation was not observed when the infusion was later stage. In contrast, infusion of anti-PrP mAb to mice infected with Chandler strain at 60, 90, and 120 dpi, prolonged the incubation periods for 14, 13.5 and 12 days, respectively. No adverse effect was observed in these mice, in addition, antibody-induced neuronal apoptosis was not observed even when the mAbs were stereotaxically inoculated into hippocampus. Although the effect was dependent on the prion strain, the mAb infusion could partly prevent the disease progression even when the infusion was started after clinical onset, suggesting that antibody therapy still be a candidate for the treatment of prion diseases.
AD C.H. Song, A. Suzuki, M. Ogino, M. Horiuchi, Graduate School of Veterinary Medicine, Hokkaido University, Japan; H. Furuoka, Obihiro University of Agriculture and Veterinary Medicine, Japan
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren: C.H. Song, H. Furuoka, A. Suzuki, R. Hasebe, A. Maeda und M. Horiuchi)