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Development of a Diagnostic Assay for Chronic Wasting Disease


<p>The stated objectives for this work were:
<br/>Continued purification of PrPSc from chronic wasting disease (CWD) central nervous system (CNS) tissue. Continued immunization of PrP knockout mice for MAb production. Initiate generation and characterization of MAbs.</p>

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<p>All transmissible spongiform encephalopathies (TSEs) are characterized by the accumulation of a pathogenic, partially protease-resistant isoform (PrPSc) of a normal host-coded glycoprotein (PrPC) of unknown function. PrPSc has been shown to correlate with infectivity and therefore serves as a marker for TSEs. Although the most sensitive method of TSE detection is the bioassay, the diagnosis of TSEs is usually accomplished by histopathology and PrPSc detection using several immunological techniques. The usefulness of these immunological assays depend on the availability of specific reagents, i.e., antibodies. Recently, a method to amplify the levels of PrPSc has been reported (Saborio et al., 2001). In addition, a protease-resistant isoform of PrPSc, termed UPrPSc, has been detected in the urine of scrapie-infected hamsters, bovine spongiform encephalopathy (BSE)-infected cattle and Creutzfeldt-Jakob disease (CJD)-infected patients (Shaked et al., 2001). Therefore, UPrPSc, if detectable in CSD-affected animals, would serve as an ideal marker for an ante-mortem test. Since it is not known if UPrPSc exists in the urine of CSD-affected animals, or at what levels, protein misfolding cyclic amplification (PMCA) (Saborio et al., 2001) is a novel technique that will be useful to explore as a method to increase the yields of protein prior to the immunological assays used for its detection.</p>

Rubenstein, Richard
New York State Institute for Basic Research
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