The use of proteomics for surrogate markers of prion infection

Transmissible Spongiform Encephalopathies are a new class of infectious diseases, as the causative agent appears to be an altered form of a normal cellular protein capable of self-replication. While these diseases originally gained attention as food-borne illnesses, it has become apparent that blood and blood-products may also transmit disease. This observation is of further concern as definitive diagnosis of TSEs relies upon post-mortem diagnostics. Ideal assays would identify the earliest stages of disease based on easily-available samples, such as blood. RTI has extensive experience in the use of animal models in biological research, and an established interest in the development of diagnostic tests for prion diseases. Our Phase I efforts have utilized advanced proteomics techniques to isolate proteins specifically altered during TSE pathogenesis in an animal model. Further, we have developed an in vitro cell-culture model of scrapie infection which can be used to define proteins of interest in TSE diagnosis. We propose to capitalize on our previous expertise in the development of monoclonal-antibody based diagnostics to specifically develop a multiplexed protein-based assay for prion disease in animals, and apply that knowledge to parallel development of blood-based diagnostics for human prion diseases.