NR AQWE
AU Kocisko,D.A.; Morrey,J.D.; Race,R.E.; Chen,J.; Caughey,B.W.
TI Evaluation of new cell culture inhibitors of protease-resistant prion protein against scrapie infection in mice
QU Journal of General Virology 2004 Aug; 85(8): 2479-83
PT journal article
AB In vitro inhibitors of the accumulation of abnormal (protease-resistant) prion protein (PrPres) can sometimes prolong the lives of scrapie-infected rodents. Here, transgenic mice were used to test the in vivo anti-scrapie activities of new PrPres inhibitors, which, because they are approved drugs or edible natural products, might be considered for clinical trials in humans or livestock with transmissible spongiform encephalopathies (TSEs). These inhibitors were amodiaquine, thioridazine, thiothixene, trifluoperazine, tetrandrine, tannic acid and polyphenolic extracts of tea, grape seed and pine bark. Test compounds were administered for several weeks beginning 1-2 weeks prior to, or 2 weeks after, intracerebral or intraperitoneal 263K scrapie challenge. Tannic acid was also tested by direct preincubation with inoculum. None of the compounds significantly prolonged the scrapie incubation periods. These results highlight the need to assess TSE inhibitors active in cell culture against TSE infections in vivo prior to testing these compounds in humans and livestock.
MH Animals; Cells, Cultured; Mice; Mice, Transgenic; PrPsc Proteins/*antagonists & inhibitors; Scrapie/drug therapy; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tannic Acid/pharmacology
AD Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. DKocisko@niaid.nih.gov
SP englisch
PO England