Amphotericin B And Analogs In Prion Disease

An analog of amphotericin B called MS-8209 has been found effective in delaying the onset of symptoms in hamsters inoculated with the causative agent of scrapie, one of the transmissible neurodegenerative diseases which include bovine spongiform encephalopathy in cattle and Creutzfeld-Jakob disease, Gerstmann-Straussler syndrome and fatal familial insomnia in humans.

All these diseases are characterized by the accumulation of an abnormal variant of a normal host protein (prion-related protein or PrP), which is accompanied by spongiosis, neuronal loss and local inflammation. No treatments have been developed to treat these diseases, largely because there is still a great deal to learn regarding their pathogenesis. However, amphotericin B has been shown to prolong the incubation time in experimental models of scrapie, but is limited by its acute toxicity and could not be used to treat a chronic illness such as CJD.

MS-8029 is five times less toxic than amphotericin B, according to Karim Tarik Adjou of the Service de Neurovirologie at France's Commissariat a L'Energie Atomique. The drug was developed by Mayoly-Spindler Laboratories of Chatou in France. Data presented at ICAAC has revealed that MS-8029 doubled the disease-free period in the hamster-scrapie model at the highest doses tested, and had a similar effect on overall survival. A decrease in the replication rate of the infectious organism was also observed. Furthermore, unlike amphotericin B, MS-8029 can achieve these effects in several model systems, albeit with variable results.