High-Throughput Screening of Compounds for Anti-Transmissible Spongiform Encephalopathy Activity Using Cell-Culture and Cell-Free Models and Infected Animals
Annual rept. 18 Jun 2005-17 Jun 2006
NATIONAL INSTITUTES OF HEALTH HAMILTON MT ROCKY MOUNTAIN LABS
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Transmissible spongiform encephalopathies are fatal untreatable neurodegenerative diseases associated with the accumulation of a disease-specific form of priori protein PrPSc in the brain. One therapeutic approach is the inhibitors of PrPSc accumulation indeed many inhibitors of PrPSc accumulation in scrapie-infected cells also have anti-scrapie activity in rodents During This year. cell line derived from deer has been chronically infected with CWD to more effectively search for agents to combat that disease Additionally two compounds That inhibit PrPSc accumulation in scrapie-infected mouse cells and CWD-infected cells. iron tetrasulfonatophenyl porphyrn FeTSP and a degenerate 40 base phosphorothioates oligonucleotide Randomer 1. were found to also have anti-scrapie activity in mice Randomer 1 mixed with infectious brain homogenate delays the onset of disease and also works prophylactically against an ip inoculated scrapie FeTSP has prophylactic activity as well as therapeutic activity against an existing scrapie brain infection which places it among a very small group of molecules with such activity Finally an antimalarial compound, mefloquine. which is an effective inhibitor of PrPSc in cell culture, did not demonstrate prophylactic anti-scrapie activity in mice This underscores the need to test promising anti-prion agents in animals prior to human trials.
- Anatomy and Physiology
- Medicine and Medical Research