Prophylactic and therapeutic effects of phthalocyanine tetrasulfonate in scrapie-infected mice.
The transmissible spongiform encephalopathy (TSE) diseases are rare, neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy, and Creutzfeldt-Jakob disease in humans. There are no effective treatments available for clinical use in humans. We now demonstrate that, in 2 different rodent models of scrapie, multiple pretreatments with the cyclic tetrapyrrole phthalocyanine tetrasulfonate (PcTS) were as effective at delaying disease as multiple treatments starting at the time of infection. At low doses of scrapie infectivity, PcTS also protected some mice from peripheral scrapie infection, even if treatment was initiated several weeks after infection. Furthermore, PcTS completely inactivated low levels of scrapie infectivity when incubated with the infectious inoculum. Thus, PcTS has a broad range of antiscrapie activities. These findings suggest that cyclic tetrapyrroles may be useful both prophylactically and therapeutically against TSE diseases in vivo, as well as for inactivation of TSE infectivity suspended in solution.
Priola
Suzette A
SA
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. spriola@nih.gov
Raines
Anne
A
Caughey
Winslow
W
D000818:Animals; D006224:Cricetinae; D007211:Indoles / Q000008:administration & dosage* / Q000627:therapeutic use*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D018621:PrPC Proteins / Q000235:genetics / Q000472:pathogenicity*; D012608:Scrapie / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control*
D007211:Indoles; D018621:PrPC Proteins; C028418:tetrasulfophthalocyanine