Abstract: 

Use of Polymyxin as an Antidote for Intoxications by Amatoxins

Background: 

Amanita phalloides is involved in the majority of human deaths from mushroom poisoning. Toxins contained in this species are a group of bicyclic octapeptides known as amatoxins, the most relevant to human intoxications being α- amanitin. α-Amanitin binds to and inhibits RNA polymerase II (RNAP II). The resulting inhibition of the transcription process causes liver and kidney necrosis. Despite several treatments that have been applied (e.g. hormones, vitamins, antibiotics, N-acetylcystein, silybin), no good antidote for poisonings was found hitherto and mortality still reaches 10-30% after poisonings.
Our findings led us to the discovery of a new clinical application for a well-established antibiotic used in hospitals against multiresistant bacteria – Polymyxin B.

Benefits: 

Polymyxin B revealed to be a specific and effective antidote for amatoxin-related poisonings. Since the clinical use of this antibiotic is well established, is may be immediately applied in Amanita phalloides poisonings.

Potential comercial use/applications: 

Antidote against intoxications by amanita mushroom species;
Potential to benefit from orphan drug status:
Potential to help Polymyxin B entering the market of hospital infections (gram-negative) in countries where it is currently unavailable