In search of an antidote against poisonous mushrooms

Pickers around the world hunt wild mushrooms to bring their earthy, nutty, and meaty flavors to the table. But once in a while, people confuse a potentially deadly variety with edible varieties.

A mushroom called death cap – Amanita phalloides – and dozens of related species containing the same toxin, alpha amanitin, account for the vast majority of mushroom poisoning deaths. And many scientists have tried to find a quick cure.

“There is no antidote,” said Terrence Delaney, a plant biologist and mycologist at the University of Vermont who studies the toxin profiles of a related fungus called the destroying angel.

In the past, such poisoning was fatal in more than half of cases, but today about 85-90% of people survive. The main treatment is hydration, as the toxin is excreted in the urine, Dr. Delaney said, and also includes electrolytes and substances to protect the liver. “But a lot of people don’t get better, and the only effective therapy is a liver transplant,” he said.

Over the years, researchers have proposed and tested several treatments, Dr. Delaney said, adding: “To be honest, none of these are convincing.

Alpha-Amanitin wreaks havoc in the body by disrupting cells’ ability to make messenger RNA. Messenger RNA builds proteins, and without new proteins, the cellular machinery shuts down. When the toxin circulates through the body, it causes significant damage to the liver.

But researchers have very few ideas about exactly how the toxin does its dirty work, said Qiaoping Wang, a pharmacologist and toxicologist at Sun Yat-Sen University in Shenzhen, China.

Dr. Wang and his colleagues are not foragers themselves. However, their job is to examine the genome to look for chains of biological events triggered by toxins, as well as molecules that block them. In a study published Tuesday in Nature Communication, they reported finding a promising molecule that appeared to prevent some of the toxic effects of alpha amanitin.

Researchers first used CRISPR, gene editing technology, to create human cells with thousands of specific genes knocked out, one by one. They then flooded the cells with alpha-amanitin and tracked those that continued to thrive. If cell life was rosier when a specific gene was turned off, they reasoned, that gene might be involved in fighting the toxin. They focused on one gene, STT3B, that seemed particularly critical for toxicity.

Next, the researchers used computer modeling to search for compounds approved by the US Food and Drug Administration that could block STT3B, coming up with 34 possible drugs. All but one fell in other cell tests.

The remaining compound, called indocyanine green (ICG), is a widely used dye for imaging liver and heart function. When Dr. Wang and his team injected mice with the toxin, followed by ICG, the animals’ recovery improved and liver damage decreased significantly.

“The exact mechanism is still unknown,” Dr. Wang said. But his team’s work so far suggests that the STTB3 gene somehow helps alpha amanitin enter cells, and that ICG prevents this step.

“It’s a spectacularly cool paper,” said Anne Pringle, a mycologist and geneticist at the University of Wisconsin, Madison, who has studied death caps for 20 years. “They do this incredible amount of work and end up with this assumption that they’ve found an antidote.”

Whether the compound will work in humans remains to be seen, but it’s a good place to start, Dr. Pringle said. “I love that they came up with a mouse model,” she said, “because it’s a lot more than what I’ve seen with some of these other ideas that have gone and come.”

The effectiveness of ICG also depended on the window between injection of the toxin and receipt of the drug; the possible remedy diminished if administered more than four hours later.

Too often people don’t know they’ve eaten a poisonous mushroom like death cap until eight or more hours later because they don’t feel sick until then, Dr. Delaney said. After suffering from intense gastrointestinal symptoms, people spend two to three days in which they feel much better. But all the while, the toxin continues to cause damage.

Dr. Delaney is part of a global network of experts who run a Facebook group called Poison Help; Emergency identification for fungi and plants.

People ask the group to identify mortars or related mushrooms. Last year, he recalls, a young boy told relatives he ate a “marshmallow” he found in the yard. The family realized what had happened, took him to the emergency room and asked the Facebook group to identify the fungus. Knowing what it was, the doctors provided appropriate care and the boy recovered.

“We’re really good at identifying Amanitas quickly and almost always give responses within 15 minutes,” he said.

Antidote or not, Dr. Delaney said, “knowing early that someone has ingested one is absolutely critical.”

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