Possible Antidote to World’s Deadliest Mushroom Discovered
A dye used in medical imaging appeared to make the death cap’s toxin less fatal to mice in a new study
The death cap is the world’s most lethal mushroom known to humans, but for years, as far as scientists knew, the poisonous fungus had no antidote.
Now, researchers say they might have found one in an unexpected source: a dye routinely used for medical imaging. In a study of human cells and mice published Tuesday in the journal Nature Communications, researchers show that the dye, called indocyanine green, could potentially act as an antidote for a toxin in the deadly mushrooms.
“Upon discovering this unexpected connection, the research team was understandably taken aback,” Qiao-Ping Wang, a co-author of the study and researcher at Sun Yat-sen University in China, tells Daniel Lawler of the Agence France-Presse (AFP).
“It’s a spectacularly cool paper,” Anne Pringle, a mycologist who studies death caps at the University of Wisconsin–Madison and did not contribute to the findings, tells the New York Times’ Alla Katsnelson. “They do this amazing amount of work and end with this hypothesis that they’ve found an antidote.”
Death caps are native to Europe, but they’re now considered an invasive species, found on every continent except Antarctica. Their caps, which range from 1.5 to 6 inches wide, can be greenish yellow, brown, tan and, in rare cases, white.
The mushrooms’ most fatal component is the toxin alpha-amanitin. It can cause vomiting, seizures, extreme liver damage and death, writes Nature News’ Saima Sidik. While death cap poisonings are rare in the United States, they cause 90 percent of mushroom-related fatalities worldwide, according to the paper.
“The death cap can, in the early growth stages, resemble some of the straw mushrooms, which are … popular, particularly in a range of Asian cuisines,” Brett Summerell, a fungi expert at the Royal Botanic Garden Sydney in Australia who wasn’t involved in the research, tells the Guardian’s Donna Lu.
Prior to looking for an antidote, the researchers first set out to investigate the mushrooms’ toxin. They knew that alpha-amanitin messes with cells’ production of RNA, but they wanted to know exactly how it does, per the New York Times. To find out, the team used CRISPR gene-editing technology to make a bunch of mutations in different genes in human cells in a lab, writes Nature News. They then exposed these cells to the mushroom toxin.
This process revealed that an enzyme known as STT3B played a role in making alpha-amanitin toxic to cells. So, the team embarked on the next phase of the research: finding a drug that could inhibit STT3B, ideally reducing the risk of alpha-amanitin to the body.
The scientists searched for potential antidotes among some 3,200 compounds approved by the U.S. Food and Drug Administration and narrowed the list down to 34. Of those, they found that indocyanine green increased the survival rate of human and mouse cells that had been given the toxin. Doctors have used indocyanine green for decades in imaging to measure liver and heart function, writes the AFP.
Then, the team tested indocyanine green as an antidote in mice. The alpha-amanitin survival rate, which was only around 10 percent in non-treated mice, jumped to about 50 percent among mice that received the antidote, per Nature News. But this effect only happened when the treatment was administered four hours after the mice were exposed to the toxin—it was not effective eight or 12 hours after exposure.
Now, the researchers want to test indocyanine green in human trials. “Further research is necessary to ascertain whether it possesses the same therapeutic benefits in human subjects,” Wang tells C&EN in an email.
But in practice, that could be tricky, because the team will need to find people who have accidentally eaten the poisonous mushrooms, per Nature News. “This kind of trial will be difficult to set up due to the rareness of this kind of poisoning,” Greg Neely, a co-author of the study and a geneticist at the University of Sydney in Australia, tells the Sydney Morning Herald’s Angus Dalton.
The fact that the treatment seemed less effective as time passed is also noteworthy. People often don’t know they’ve eaten a poisonous mushroom for more than eight hours, because it takes that long for them to start to feel sick, Terrence Delaney, a mycologist at the University of Vermont who did not contribute to the study, says to the New York Times. “Early knowledge that someone has ingested one of these is absolutely essential,” he tells the publication.