Exposure of the EU population to the BSE prion strain raises serious concerns that a major epidemic of variant CJD will follow. The possibility of iatrogenic transmission of pre-clinical disease by blood products and surgical instruments poses further challenges. In view of this, development of post-exposure strategies against prion disease is mandatory. As an established European consortium, we propose an integrated multi-disciplinary approach to achieve this. We will validate our existing transgenic mice as standardised in vivo models of human prion disease to evaluate the effect of candidate therapeutics on central and peripheral pathogenesis. We will explore novel biochemical, cellular and immunological targets of intervention. Because of the extremely prolonged incubation periods of prion disease in humans, there is a window of opportunity to develop treatments to abort such an epidemic.