update 2013-04-04: this post is deprecated, please see polyene antifungal drugs for prion disease instead for a more complete treatment of this topic.

Recently @3 learned of another potential prion therapeutic from that most reliable of sources: the TV show House.  Apparently a patient came in with prion disease and Dr. House directed the others to “put him on amphotericin,” just like that, as though everyone knew that’s how you treat prion disease.  (Before you get too excited about amphotericin, evidently House has also previously prescribed surgery, radiation and chemotherapy for prion diseases).

But it turns out that unlike the other options mentioned above, amphotericin actually is a potential prion therapeutic that has been under study for some time.  It’s currently approved as an anti-fungal medication, although apparently it is toxic enough to have earned the nickname “ampho-terrible” (mechanism of toxicity: creates pores in your cell membranes. Awesome, right?)  Most of the papers I was able to find online are from over 10 years ago, so perhaps scientists have since lost interest in this drug, but it seems that it has been shown to inhibit PrPSc formation in cell culture [Mange 2000a],[Mange 2000b] and prolong incubation in scrapie-infected hamsters [Pocchiari 1987].  Mange (2000a) even proposes a mechanism of action:

Its action seems related to a modification of PrP trafficking through the association of this glycosylphosphatidylinositol-anchored protein with detergent-resistant microdomains.

And finally, there’s been some work on less toxic analogues.  MS-8209 showed success in hamsters [Adjou 1999],[Adjou 2000], and finally, (and this is the one more recent work I found), 16-19B has proven both more effective and less toxic than AmB in mouse cell culture [Soler 2008].

Sounds good, right?  I would love to know where this research stands today.