Evaluation of new cell culture inhibitors of protease-resistant prion protein against scrapie infection in mice.
In vitro inhibitors of the accumulation of abnormal (protease-resistant) prion protein (PrP-res) can sometimes prolong the lives of scrapie-infected rodents. Here, transgenic mice were used to test the in vivo anti-scrapie activities of new PrP-res 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.
Kocisko
David A
DA
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Morrey
John D
JD
Institute for Antiviral Research, Animal, Dairy, and Veterinary Sciences Department and Biotechnology Center, Utah State University, Logan, UT 84322-4700, USA.
Race
Richard E
RE
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Chen
Jiancao
J
Chengdu Jinniu Institute, Food Bureau of Sichuan Province, Chengdu Sichuan, China.
Caughey
Byron
B
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
D000818:Animals; D002478:Cells, Cultured; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors*; D012608:Scrapie / Q000188:drug therapy
D047348:Hydrolyzable Tannins; D018620:PrPSc Proteins