Researchers find readily available potential antidote for death cap mushrooms

After a day spent foraging in the field, you cook up your delicious mushroom bounty. However, like thousands of other people around the world every year, you’ve accidently ingested a death cap (Amanita phalloides)

Just 30 grams is enough to kill a human, and those who are poisoned by the mushroom can experience horrific symptoms, including liver and kidney failure. Although the mortality rate is unknown, it is thought to be between 10% and 30%, and there’s currently no antidote.

Now a team of researchers has found that a substance already approved by the US Food and Drug Administration (FDA) could reduce the toxicity of the deadly ‘shroom, although more research will be needed to confirm.

“Among all poisonous mushrooms, death caps are responsible for more than 90 percent of deaths,” the researchers write in their new paper in Nature Communications.

“Amatoxin poisoning is commonly associated with poor outcomes, mainly owing to the irreparable acute failure of the liver or kidney.”

“We demonstrate that indocyanine green is effective in blocking the toxic effect of α-amanitin in cells, liver organoids, and male mice, resulting in an overall increase in animal survival.”

Death caps are found in many places across the world, including Europe, Australia and America, and unfortunately because they look similar to the paddy straw mushroom and the white Caesar, they are occasionally mistaken and eaten.

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The researchers of the new paper looked specifically at the most fatal toxin inside the death cap mushroom, α-amanitin.

By using the ‘cut and paste’ genetics tool CRISPR/Cas9 the researchers first looked at which genes were important when α-amanitin enters the system. They discovered that another genetic pathway called N-Glycan biosynthesis and a protein called STT3B – a key component to that pathway – was also heavily affected by α-amanitin.

After homing in on the protein, the researchers did a virtual drug screen to find out which compounds could inhibit STT3B. They discovered that a cyanine dye called indocynanine green – which has already been approved by the FDA – could prevent liver toxicity.

When tested on human cell lines and mice, the dye increased the probability of survival significantly. In the mice, the probability of survival went from under 25% at the 10-day mark for the mice that just had the α-amanitin to 50% for those that were also given indocynanine green.

Unfortunately, this is not completely solved yet. More research will need to be done, particularly in the safety for humans, and when to best give these treatments, however this is an important step.

“We observed that indocynanine green loses its treatment effect on α-amanitin toxicity when it was delivered 8 and 12 h post α-amanitin injection,” the researchers write.

“This may be because α-amanitin has caused irreversible damage during early hours of cytotoxicity, which is unable to be salvaged by indocynanine green treatment. This suggests that ICG should be given as early as possible during treatment.”

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