Differential effects of a new amphotericin B derivative, MS-8209, on mouse BSE and scrapie: implications for the mechanism of action of polyene antibiotics.
Mice were infected intracerebrally with the bovine spongiform encephalopathy (BSE) or the scrapie agent and treated during 8 weeks postinfection to test the protective effect of a new amphotericin B (AmB) derivative, MS-8209, in experimental transmissible spongiform encephalopathies. The results show that (i) the treatment prolonged the incubation period of both BSE-infected and scrapie-infected mice, (ii) MS-8209 and AmB were much more efficient in delaying the onset of scrapie than that of BSE, and (iii) a delay in Prp-res (proteinase K-resistant prion protein) and GFAP (glial fibrillary acidic protein) accumulation was observed in the brains of scrapie-infected mice, but was not significant in BSE-infected mice. The analysis of the molecular and clinical results strongly suggests a common mechanism of action of this category of drugs on the different transmissible spongiform encephalopathy strains. This could be due to an interaction with the PrP transconformation process leading to the formation of PrP-res.
Adjou
K T
KT
Départment de Recherche Médicale, Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France.
Demaimay
R
R
Lasmézas
C I
CI
Seman
M
M
Deslys
J P
JP
Dormont
D
D
D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents; D000998:Antiviral Agents / Q000627:therapeutic use*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D016643:Encephalopathy, Bovine Spongiform / Q000188:drug therapy*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011090:Polyenes; D018620:PrPSc Proteins / Q000378:metabolism; D012608:Scrapie / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D011090:Polyenes; D018620:PrPSc Proteins; C074660:MS 8209; D000666:Amphotericin B