Looking for an antidote to poisonous mushrooms

Collectors around the world hunt wild mushrooms to bring their earthy, nutty, meaty flavors to the table. But occasionally people mistake a potentially lethal variety for the edible one.

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

“There’s no antidote,” says Terrence Delaney, a plant biologist and mycologist at the University of Vermont who studies the toxin profiles of a related mushroom called the Destroying Angel.

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

Over the years, researchers have proposed and tested various treatments, said Dr. Delaney, adding, “To be honest, none of those are convincing.”

Alpha-amanitin wreaks havoc in the body by messing up the cells’ ability to make messenger RNA. Messenger RNA builds proteins, and without new proteins, the cell’s machinery grinds to a halt. As the toxin circulates through the body, it causes extensive damage to the liver.

But researchers have very little idea of ​​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 collectors themselves. However, they are examining the genome to look for chains of biological events triggered by toxins, as well as molecules that block them. In a study published on Tuesday, they reported in Nature Communication that they had found a promising molecule that appeared to prevent some of the toxic effects of alpha-amanitin.

The researchers first used CRISPR, the gene-editing technology, to create human cells where thousands of specific genes were knocked out one by one. They then flooded the cells with alpha-amanitin and monitored which continued to thrive. If the cells’ lives were brighter when a specific gene was deactivated, they reasoned, that gene might be involved in fighting the poison. They narrowed down to one gene, STT3B, which seemed especially crucial for toxicity.

Next, the researchers used computer modeling to look for U.S. Food and Drug Administration-approved compounds that could block STT3B, coming up with 34 potential drugs. All but one fell out on further tests on cells.

The remaining compound, called indocyanine green (ICG), is a dye commonly used to create images of liver and heart function. When dr. Wang and his team injected the toxin into mice, followed by ICG, improved the animals’ recovery and significantly reduced liver damage.

“The exact mechanism is still unknown,” said Dr. Cheek. 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 an incredible amount of work and end up hypothesizing that they’ve found an antidote.”

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

The effectiveness of the ICG also depended on the time frame between injection of the toxin and receipt of the drug; the potential cure diminished if given more than four hours later.

Too often, people don’t know they’ve eaten a poisonous mushroom like the deadly cap until eight hours or more later, because they don’t feel sick until then, said Dr. Delaney. After some intense gastrointestinal symptoms, people go through two to three days where they feel much better. But all the while, the poison continues to wreak havoc.

Dr. Delaney is part of a global network of experts who run a Facebook group called Poison aid; Emergency Identification for Mushrooms & Plants.

People ask the group to identify death caps or related mushrooms. Last year, he recalls, a boy told relatives that he had eaten a “marshmallow” he found in the garden. Realizing what had happened, the family took him to the emergency room and asked the Facebook group to identify the mushroom. Knowing what it was, the doctors provided proper care and the boy recovered.

“We are very good at identifying Amanitas quickly and almost always reply within 15 minutes,” he said.

Antidote or not, said Dr. Delaney, “Early knowledge that someone has taken one of these is absolutely essential.”