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 encephal opathy (BSE) or the scrapie agent and treated during 8 weeks postinfec tion to test the protective effect of a new amphotericin B (AmB) deriv ative, MS-8209, in experimental transmissible spongiform encephalopath ies. The results show that (i) the treatment prolonged the incubation period of both BSE-infected and scrapie-infected mice, (ii) MS-8209 an d AmB were much more efficient in delaying the onset of scrapie than t hat 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 significa nt in BSE-infected mice. The analysis of the molecular and clinical re sults strongly suggests a common mechanism of action of this category of drugs on the different transmissible spongiform encephalopathy stra ins. This could be due to an interaction with the PrP transconformatio n process leading to the formation of PrP-res.