New hope for an antidote to death cap mushrooms and other poison fungi

They don't call it the "death cap" mushroom without good reason. It's one of the most poisonous mushrooms in the world. Eating only half a cap can shut down your liver – and if you don't get medical attention fast enough, that shroom just might turn out to be your last meal.

Mushroom poisonings are tough to track reliably, but some scientists estimate that they cause about 10,000 illnesses and 100 deaths a year globally. Until now, effective treatments for death cap poisonings were few and far between with no proven antidote available.

But in new research published this week in Nature Communications, a team of Chinese and Australian scientists reports that they may have found an antidote for death cap mushroom poisoning – and it's a widely available drug that already has FDA approval.

So far, the drug has only been shown to be effective in mice, but it's a discovery that could help prevent deaths from poisoning by death caps and by many other poisonous mushroom species found around the world.

Mushroom poisoning is often a case of mistaken identity

While foragers should take heed of regular warnings by health officials about the dangers of poisonous mushrooms, most mushrooms are not dangerous. In reality, "the vast majority are completely innocuous," says Marin Brewer, a mycologist at the University of Georgia. "There's a really small percent that are tasty gourmet edibles, and then a really small percent that are poisonous."

But to the untrained eye, the unassuming white cap and stalk of the death cap can be confused with tasty edible mushrooms such as the paddy straw. Death caps grow widely in Europe and western North America, and can easily fool foragers from countries where death caps don't exist but the lookalikes do.

Those most susceptible to mushroom poisoning are often immigrants, says Anne Pringle, a mycologist and expert on death cap mushrooms at the University of Wisconsin, Madison.

"There was a Ukrainian family and they thought, 'Oh, [a death cap] looks like this thing we have back in Ukraine,'" she says. We tend to underestimate how diverse mushrooms are, Pringle says, thinking that "the thing that's in Massachusetts is the thing that's in Ukraine. And then if you make that mistake, then you can end up eating a death cap."

The death cap mushroom, Amanita phalloides, is perhaps the most infamous of the deadly mushrooms. Along with destroying angels and a few other species, they form the group known as lethal amanitas, which are responsible for 90% of fatalities by mushroom poisoning around the world.

The lethal amanitas all produce a toxin called ɑ-amanitin, also known as AMA, which attacks the liver and kidneys. It essentially stops the cells in those organs from making proteins, causing the cellular processes to grind to a halt.

It can take hours before someone who mistakenly eats a mushroom containing AMA to feel sick. Initially, their symptoms typically include "horrible gastrointestinal problems, vomiting and diarrhea, and people are usually extremely dehydrated," Brewer says.

Few effective treatments exist for death cap poisonings. Doctors sometimes give patients, "a large dose of penicillin G," Brewer says. "They didn't know exactly how that worked, but they thought maybe it stimulated the liver." There is also a newer drug derived from the milk thistle plant called silibinin, but Brewer says that, "it's still undergoing FDA trials."

And if those treatments didn't work, "quite often they would have to prepare for a liver transplant," Brewer says.

Finding an antidote using 'brute force'

The discovery of a potential antidote for death cap poisoning came seemingly out of nowhere. For Pringle and Brewer, who were not involved with the antidote discovery, the results came as a surprise.

"I had no idea this [the discovery of a potential antidote] was happening," Pringle says.

The research team took human cells and edited them to break individual genes. Then they fed them the AMA toxin to see which ones survived. One of those surviving mutants had a broken STT3B gene, which the researchers hypothesized might help transport the toxin into human cells.

So the team used a computer program to look for FDA approved drugs that might block STT3B from working. They found a match in the compound ICG, an iodide based dye that has been used in humans since 1956 to help diagnose diseases in the eye.

When they gave mice ICG after they had been poisoned with AMA, the drug had a clear protective effect in the livers of the mice, and the rates of survival improved from about 20% to 50%.

This led the team to conclude that "ICG is an effective antidote for treating AMA toxicity in mice." It's an encouraging sign – but we still don't know how effective of an antidote it is in humans.

"If the word antidote is used to mean, like, you give it and everyone recovers, it's probably not quite there yet, because you haven't tested it in humans," says Pringle. "Human trials are tricky when it comes to this kind of work because you can't feed people mushrooms and then try to cure them."

The only way to test the effectiveness of ICG is to wait until someone comes into a hospital after having eaten a death cap. Then doctors can give the patient the drug and see if it helps.

ICG could could be effective against more than just death caps

With the caveat that human trials are still needed, Pringle is optimistic that the drug could help treat poisonings from all kinds of mushrooms around the world.

"There are many species of lethal Amanitas. So there are other Amanitas for which this [drug] would be useful," she says.

In fact, Pringle says other cases of mushroom poisoning are often misattributed to death caps. "All the poisonings in huge chunks of the continent of Africa have nothing to do with death caps because they don't grow there. So those poisonings are about [other kinds of mushroom]," she says.

But since many mushrooms across the world produce the lethal AMA toxin, ICG hypothetically should help treat poisoning from them all.

"There just isn't this broader knowledge that each region has its own endemic fungal biodiversity. Death caps are not everywhere. They are native to some places [Europe], invasive in others [North America], and totally absent from other places." Pringle says.

And for those who are worried about accidentally ingesting a poisonous mushroom when they go out foraging, Brewer says to, "go out with people who are experts or find a local mushroom club. And if you're ever in any doubt, throw it out. Don't ever risk it."

Copyright 2023 NPR. To see more, visit https://www.npr.org.