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Contenido archivado el 2024-05-29

An integrated immunological and cellular strategy for sensitive TSE diagnosis and strain discrimination


Prion infections, or Transmissible Spongiform Encephalopathies (TSEs), result in progressive, fatal neurodegeneration. No effective therapies are available, and medical interventions, possibly including blood transfusions, have resulted in human-to-human transmission of prions. However, no biomarkers are available for preclinical diagnosis of prion infection in body fluids. All approved methods of diagnosis rely exclusively on detection of pathological prion protein (PrPSc), which may not be present in all TSEs. The TSEUR consortium proposes to develop, validate, and exploit innovative reagents and technologies that will address the above problems in three areas: (1) enhanced detection of PrPSc, (2) direct measurement of prion infectivity, and (3) validation of new TSE biomarkers in body fluids. Each partner brings into TSEUR a substantial body of existing knowledge and data, including a powerful new panel of picomolar-affinity anti-PrP monoclonal antibodies to a variety of PrP domains, which will provide the basis for highly sensitive detection of PrPSc and discrimination of prion strains ('epitope coding'). We will field-test the validity of our recently identified secreted surrogate markers, whose levels are profoundly increased in preclinical prion infections, for identifying potentially contaminated body fluids. Immuno-PCR technology will be explored as a means to enhance the sensitivity threshold of each assay. Finally, we will extend the scrapie cell assay technology for rapid and sensitive detection of bona fide prion infectivity in a variety of paradigms. Ongoing work indicates that all workpackages are highly feasible. The TSEUR program will develop innovative diagnostic technologies addressing the current gaps in prion detection, with the ultimate goal to enhance the safety of the blood supply, to provide minimally invasive diagnostics of human and animal TSEs and to develop highly sensitive tools for discrimination of pr

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