Composition and Methods for Enhancing and Detecting Prion Protein

Prion diseases such as Creutzfeldt Jakob Disease (CJD), bovine spongiform encephalopathy (BSE), chronic wasting disease (CWD), and scrapie are fatal, infectious, neurodegenerative diseases that occur in humans and other mammalian species. The conversion of a normal host prion protein (PrP) into a protease-resistant state (PrPres) is the most specific biochemical alteration in individuals affected by prion disease. A rapid and sensitive diagnostic test for early detection of prion disease is urgently needed to help control the spread of prion diseases such as CWD and BSE throughout the world. Such a test could be used to identify newly infected cases, facilitating public health programs aimed at eradicating these diseases.



Tests based on measurement of prion infectivity are highly sensitive but slow, taking months to complete. In contrast, tests based on PrPres detection are rapid, but less sensitive than bioassay. Biochemical amplification of PrPres could in principle be used to increase the sensitivity of tests based on PrPres detection, such as the standard protease digestion-Western blot assay, filter retention assay, ELISA, or conformation dependent assay.



Researchers at Dartmouth Medical School have recently discovered that biochemical amplification of PrPres is stimulated by addition of species-specific preparations of RNA molecules. Notably, RNA molecules derived from mammalian species stimulated PrPres amplification, but similarly prepared RNA molecules derived from invertebrate species did not stimulate PrPres amplification. A variety of other control polyanions, such as heparan sulfate and DNA, also did not stimulate PrPres amplification.



The major commercial application of this discovery is enhanced sensitivity for prion disease diagnostic testing. Other potential applications include development of novel therapeutic and disinfectant agents effective against infectious prions.



These findings are claimed in the published United States Patent Application Nos. 10/553,591 and 11/327,993. We are seeking an industrial partner to further refine and market this technology. (Ref:J230

Type of Offer: Licensing



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