Transmissible Spongiforme Encephalopathy in non-human primate model after intraperitoneal sCJD-, vCJD-, and BSE-inoculation in the rhesus monkey (Macaca mulatta)

• Applicant: Professor Dr. Franz-Josef Kaup
• Subject Area: Veterinary Medical Science
• Term: from 2005 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5442913

...In our project aspects of organismic biology and molecular pathology are combined. Our rhesus monkeys represent an animal model to assess early changes of behaviour in a way that is not feasible in experimental rodent prion infection models. Health control is tight because of the excellent expertise on macaques of our in-house veterinarians and animal caretakers. For the first time, telemetry is used in a prion infection model as a means to assess circadian rhythm, activity (sleep/wake-cycles) and body core temperature. This experimental approach offers the possibility to document ablation or changes of activity and behaviour as early markers for the infection and progression of the diseases. Extensive preinoculation studies have been performed, i.e. a large data colllection based on video, telemetry and visual observation already exists. Current work includes establishing mRNA detection for the putative surrogate marker gene alpha-haemoglobin-stabilizing-protein (AHSP) by RT-PCR and realtime RT-PCR. An archive with collected blood and bolld components, skin biospy specimens and lymph node specimens has already been established for future transmission and infection studies (8. Appendages). The existing project(s) enable(s) us to rapidly react on actual developments and scientific insights in prion research such as collection of cells or tissues suspected to play a role in replication and propagation of prions. Although we have a limited number of animals some might be used for intervention expreiment as already suggested by A. Aguzzi and J. Collinge (PrP decoys and monoclonal antibodies, respectively). Even if animals stay in a subclinical stage application of any therapeutic intervention measure could be investigated. For instance, there is an upcoming controversial debate between leading groups as to the benefit of monoclonal antibodies by reducing endogenous PrP or to an induction of loss of function of cellular PrP as a factor of neuronal survival (recent reports during the winter meeting Growth and Death in the Nervous System in St. Moritz from March 24-28, 2004).

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Walter Bodemer