Mortal combat

Researchers have discovered a potential antidote to death cap mushroom poisoning.

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While it looks innocent enough—and reportedly tastes good—the death cap (Amanita phalloides) is responsible for about 90 per cent of fungi-related deaths worldwide. Within a day or so of munching on this mushroom, you’ll end up seriously ill with intense gastrointestinal symptoms—sometimes proving lethal.

Amanita phalloides pops up across New Zealand, often growing in association with oak and chestnut trees. While poisonings are rare here, they do occur: in 2020, a Waikato doctor suffered permanent liver and kidney damage after eating a foraged death cap, and in 2005, another person required a liver transplant.

Death caps contain a toxin called a-amanitin, which attacks the liver and kidneys. Figuring out how a-amanitin works at a cellular level meant that researchers could find a way to block its mechanism: an antidote. First, they screened human cell samples with different genes switched off, applying a-amanitin to see which samples would survive. Only one did, and that let them pin down a protein called STT3B.

In the next step, the researchers identified a drug that would block STT3B, thereby restricting the activity of the mushroom’s toxin. Indocyanine green, a compound already approved by the US Food and Drug Administration for medical diagnostic tests, showed promise.

Through testing in mice and human cells, the researchers showed that indocyanine green is effective at blocking the toxic effects of the death cap poison. Healthy mouse liver cells (shown below, at left) are destroyed by a-amanitin (middle column) but survive when indocyanine green is administered (at right). Further research is needed to assess the safety of indocyanine green in humans.

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