Drug Therapy For Prion Diseases?

A derivative of amphotericin B developed by French researchers has shown promise in the treatment of animal models of prion disease. Prions are thought to be the causative agent in a range of neurodegenerative diseases, such as scrapie and bovine spongiform encephalopathy in livestock and Creutzfeld-Jakob disease in humans.

Amphotericin B is one of the rare agents that have shown efficacy in animal models of prion diseases, but its use is limited to the early stages of infection by acute toxicity. The new compound, MS-8209, has a five-fold lower toxicity than the parent compound and can be given at the high doses needed to demonstrate a therapeutic effect.

The researchers tested amphotericin B and MS-8209 in experimentally-inoculated hamster and mouse scrapie. Interestingly, treatment with these polyene antibiotics did not modify expression of prion protein (PrP) messenger RNA, although PrPsc accumulation (the abnormal isoform of the protein) was reduced after 30 days treatment. Thus, amphotericin B and MS-8209 seem to interfere with the production of PrPsc at the post-translational stage and interfere with infectivity, they noted. The effect of continuous treatment with the two drugs, and especially MS-8209, enhanced survival time in the experimental animals in a dose-dependent fashion.