Drug discovery: Insights into box jellyfish venom reveal potential antidote

An antidote to the venom of the box jellyfish Chironex fleckeri that suppresses tissue death and pain in mice has been identified. The findings, reported in a Nature Communications article published this week, suggest the technique used could be applied to toxins from other animals.

The box jellyfish is one of the most venomous animals in the world. Exposure to its venom causes extreme pain and can lead to death within minutes after severe exposure, but the mechanisms leading to this rapid action are unknown. Current treatments have limited effects, and none are able to directly target pain or local tissue death - the most common clinical outcomes of venom exposure. A major obstacle to the development of new treatments is the limited molecular understanding of venom action.

Greg Neely and colleagues performed a genome-wide CRISPR screen to identify genes required for host cell death after exposure to C. fleckeri venom. They identified several genes essential to venom cell toxicity, including those involved in cholesterol biosynthesis, and showed that interfering with these genes increased resistance to box jellyfish toxin. In addition, administration of 2-hydrosypropyl-β-cyclodextrins, which modulates cholesterol and has been used in humans to treat Niemann-Pick Disease, reduced pain and blocked tissue death in mice when administered up to 15 minutes after exposure to the toxin.

By uncovering the cellular pathways involved following toxin exposure, the authors conclude that their findings provide information that could be used to design additional jellyfish venom antidotes.