Late treatment with polyene antibiotics can prolong the survival time of scrapie-infected animals.
Amphotericin B (AmB) is one of the few drugs able to prolong survival times in experimental scrapie and delays the accumulation of PrPres, a specific marker of this disease in the brain in vivo. Previous reports showed that the AmB effect is observed only if the drug is administered around the time of infection. In the present study, intracerebrally infected mice were treated with AmB or one of its derivatives, MS-8209, between 80 and 140 days postinoculation. We observed an increased incubation time and a delay in PrPres accumulation and glial fibrillary acidic protein gene expression. Treatment starting at 80 days postinoculation was as efficient as long-term treatment starting the day of inoculation. Our results indicate that polyene antibiotics may interfere, throughout the course of the experimental disease, with the propagation of the scrapie agent.
Demaimay
R
R
Commissariat à l'Energie Atomique, Département de Recherche Médicale, Service de Santé des Armées, Fontenay aux Roses, France. rdemaimay@atlas.niaid.nih.gov
Adjou
K T
KT
Beringue
V
V
Demart
S
S
Lasmézas
C I
CI
Deslys
J P
JP
Seman
M
M
Dormont
D
D
D000595:Amino Acid Sequence; D000666:Amphotericin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011090:Polyenes / Q000494:pharmacology*; D018620:PrPSc Proteins; D011817:Rabbits; D012608:Scrapie / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D000900:Anti-Bacterial Agents; D011090:Polyenes; D018620:PrPSc Proteins; C074660:MS 8209; D000666:Amphotericin B