NR AWHC
AU Holznagel,E.; Yutzy,B.; Coulibaly,C.; Deslys,J.P.; Hahmann,U.; Stuke,A.; Hunsmann,G.; Löwer,J.
TI Simian vCJD: course of the disease
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-27
PT Konferenz-Poster
AB In the study referenced, we present clinical and laboratory data from a longitudinal study of 18 Cynomolgus monkeys dosed with BSE that ultimately developed simian vCJD. Animals (female, born in 1997, homozygous for methionine at codon 129 Prnp) were dosed with a brain homogenate mixture derived from British BSE cattle. Monkeys were either dosed intracerebrally or orally. The incubation period was defined as the time period from the inoculation time point until the first behavioural changes. The incubation period in monkeys intracerebrally dosed with 5 mg BSE each was 1837 dpi (median). In an ongoing study, the earliest time point of simian vCJD among the orally dosed monkeys was 1540 dpi. The first indication of ataxia occurred 1-4 months after the onset of behavioural changes. However, shorter incubation periods were obtained when the drop in body weight was used. Here, the onset of the disease occurred 60-140 days earlier. Interestingly, the drop in body weight was accompanied by the decline in blood cells expressing a 37kDa-non-integrin laminin receptor precursor. 14-3-3 protein-CSF samples were found during the period of CNS symptoms but not at earlier time points. Diseased monkeys were sacrificed 1 month after the onset of ataxia. At necropsy, the brain was taken and one hemisphere was fixed either in Carnoy's fixative or in buffered paraformaldehyde. Lesion profiles were determined in hematoxylin-eosin stained serial sections. Tissue samples from defined areas (medulla oblongata, pons, nuc. caudatus hypothalamus, thalamus and other areas) were taken from coronary sections of the other hemisphere, Varying amounts of PrPres were found by western immunoblot using a number of different monoclonal antibodies against PrP. In conclusion, in simian vCJD, statistically significant changes occur long before brain damage is detectable. Body weight loss is a biomarker suitable for defining the onset of the disease. The work referenced was performed in partial fulfilment of the study "BSE in primates" supported by the EU (QLK1-2002-01096).
AD E. Holznagel, B. Yutzy, C. Coulibaly, J. Löwer: Paul-Ehrlich-Institut, Langen, Germany; J.-P. Deslys: Commissariat à l'Energie Atomique (CEA), Fontenay-aux-Roses, France; U. Hahmann, A. Stuke: German Primate Centre (DPZ), Göttingen, Germany
SP englisch
PO Italien