Seeking an antidote for poisonous mushrooms

Hunter-gatherers around the world hunt wild mushrooms to bring their earthy, nutty, meaty flavor to the table. But sometimes people mistake potentially lethal varieties for edible varieties.

Mushrooms called deathcap (genus Amanita) and dozens of related species that contain the same toxin, alpha-amanitin, account for the majority of deaths from mushroom poisoning. 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 related mushrooms called angels of destruction.

In the past, more than half of cases of such poisonings were fatal, but now about 85-90 percent of people survive. Toxins are excreted in the urine, so the main treatment is hydration, which includes electrolytes and liver-protective substances, Dr. Delaney says. “But many people do not get better and the only effective treatment is a liver transplant,” he says.

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

Alpha-amanitin wreaks havoc in the body by disrupting the cells’ ability to make messenger RNA. Messenger RNA builds proteins, but without new proteins, the cellular machinery stops. As toxins circulate through the body, they cause extensive damage to the liver.

But researchers know very little about exactly how the toxin does its dirty work, said Qiaoping Wang, a pharmacologist and toxicologist at Sun Yat-sen University in Shenzhen, China. rice field.

Dr. Wang and his colleagues are not collectors themselves. But their job is to scan the genome for the cascade of biological events triggered by toxins and the molecules that stop them.and research published In a Nature Communication Tuesday, they report the discovery of a promising molecule that may prevent some of the toxic effects of α-amanitin.

The researchers first used the gene-editing technique CRISPR to create human cells with thousands of specific genes knocked out one by one. We then filled the cells with alpha-amanitin and tracked which cells continued to proliferate. If cells found life easier when a particular gene was inactivated, they reasoned, that gene might be involved in fighting toxins. They narrowed it down to one of her genes, STT3B, that appeared to be particularly important for virulence.

The researchers then used computer modeling to search for compounds approved by the U.S. Food and Drug Administration that could block STT3B, coming up with 34 possible agents. Further testing of the cells failed all but one.

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

“The exact mechanism is still unknown,” said Dr. Wang. However, his team’s previous work suggests that the STTB3 gene somehow assists α-amanitin in entering cells, and that ICG interferes with this step.

“This is an amazing paper,” says Ann Pringle, a mycologist and geneticist at the University of Wisconsin-Madison who has been studying mortality limits for 20 years. “They did an amazing amount of research and ended up with the hypothesis that they had found an antidote.”

It’s not yet known if the compound will work in humans, but it’s a good starting point, Dr. Pringle said. “I love that they’ve gone as far as the mouse model because it’s so much better than what I’ve seen with some other ideas that have come and gone. she said.

The efficacy of ICG also depended on the time window between toxin injection and drug administration. After 4 hours or more of administration, the available treatments taper off.

Dr. Delaney says that very often people don’t realize they’ve eaten a poisonous mushroom like deathcap until eight hours or more have passed before they feel sick. After suffering from severe gastrointestinal symptoms, I feel much better in a few days. But all the while, the toxin continues to do damage.

Dr. Delaney is part of a global network of professionals called the Facebook Group. Poison help; emergency identification of mushrooms and plants.

People ask groups to identify deathcaps and related mushrooms. He recalled a boy telling relatives last year that he ate a “marshmallow” he found in the garden. When his family realized what had happened, they took him to the emergency room and asked a Facebook group to identify the mushroom. Doctors who found out what it was, provided appropriate treatment and the boy recovered.

“We are very good at identifying amanita very quickly, most of the time within 15 minutes,” he said.

Whether it’s an antidote or not, Dr. Delaney said, “It’s absolutely essential to know early that someone has ingested one of these.”