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Tempting but toxic mushrooms? Drug promises new cure

The toxic death cap mushroom, known technically as Amanita phalloides, can destroy the livers of people who eat it. A drug being studied in the U.S. derived from milk thistle seeds may help.
The toxic death cap mushroom, known technically as Amanita phalloides, can destroy the livers of people who eat it. A drug being studied in the U.S. derived from milk thistle seeds may help.Sean Gallup/Getty Images

When unusually rainy weather near Washington, D.C., produced a bumper crop of mushrooms last fall, it also sparked a scary surge in mushroom poisonings.

Four people in two weeks showed up at area hospitals with life-threatening liver damage after picking and eating tempting fungi that turned out to be toxic.

“We thought it was a good mushroom because it sprung up in our backyard,” one of the victims, Frank Constantinopla, 49, of Springfield, Va., told reporters at the time.

But the treat Constantinopla plucked and stir-fried with noodles was actually the feared death cap toadstool responsible for most mushroom fatalities worldwide. Within days, he was in a local hospital on the brink of liver failure.

Constantinopla’s liver -- and his life -- were saved, however, by an investigational drug derived from an old folk remedy: the seeds of the milk thistle plant, a doctor who treated him told an expert panel on Sunday. As mushroom foraging continues through the spring, fungi fans should take note.

“It’s a treatment and well-described in our hepatology [science of the liver] literature, but it’s not readily available,” said Dr. Jacqueline Laurin, a liver transplant specialist at the Georgetown Transplant Institute, part of MedStar Georgetown University Hospital. “We need to make it easier for people to get it.”

Known as Legalon, the drug is an intravenous form of silibinin, milk-thistle extract, which may turn out to be an antidote to mushroom poisonings that sicken hundreds of people in the U.S. every year, sometimes leading to death.

It’s being tested in a clinical trial led by Dr. Todd Mitchell, a California doctor who developed the "Santa Cruz Protocol" for treating mushroom poisoning. The trial is sponsored by German drugmaker Madaus Inc., which already sells the product approved in Europe.

Silibinin, a drug derived from the seeds of the milk thistle plant, may help save people with toxic mushroom

Nearly 6,000 people reported contact with suspicious mushrooms in 2010, and more than 1,300 people got sick, according to latest figures from the American Association of Poison Control Centers. Some 500 people suffered moderate to major injuries and at least one person died.

Most of the victims were sickened by the Amanita phalloides -- death cap -- varieties that produce amatoxins, which shut down liver function.

Laurin presented the four cases in quick succession that alarmed Georgetown doctors during Digestive Disease Week, a gathering of experts in the field. The study was conducted through the Georgetown University Medical Center.

When Constantinopla was transferred with incipient (or early stage) liver failure, Laurin and her team got in touch with Mitchell, who is a primary care doctor at Dominican Santa Cruz Hospital in California. Mitchell said he advised Laurin about how best to treat the patient. His protocol recommends aggressive hydration and drainage of the bile duct in addition to IV silibinin.

Stores of the drug were found in Pittsburgh and delivered by plane and courier. Within hours, Constantinopla was treated under an exemption of Food and Drug Administration rules that allow a one-patient, one-time use of an unapproved drug.

But when another victim showed up with dire symptoms after eating mushrooms, followed by two more, the hospital was forced to convene an emergency meeting of its institutional review board to grant approval for those patients to be treated, too.

“We knew it wasn’t out of the realm of possibility that another person could show up with mushroom poisoning,” Laurin said.

Mitchell, who has become an expert in amatoxin poisoning, got interested in silibinin in 2007, when he was the emergency room doc who treated six members of a Mexican family who became critically ill after consuming tacos made with toxic mushrooms.

“They had eaten the mushrooms after picking them at a state park outside of Santa Cruz,” he said.

No one in the U.S. had silibinin, so Mitchell had to request that the FDA allow emergency import of enough of the drug to treat the clan. The family’s 82-year-old grandmother died, but others were saved by the milk thistle treatment, including a 25-year-old man who was listed for a liver transplant.

Mitchell was impressed; without good treatment, the mortality rate for amatoxin poisoning can be 50 percent. The toxins basically shut down the protein-making apparatus of cells in the liver, causing the organ to fail.

“The antidote blocks the entry of amatoxin into the liver cell,” he explained.

Despite the fact that Mitchell is not a clinical toxicologist ("I'm just a primary care guy," he said), he decided to try to make sure the drug -- and the protocol that goes with it -- are available in the U.S.

So far, Mitchell's trial includes some 44 patients treated with silibinin and the protocol. Of those, five have died, but Mitchell said the procedure wasn't followed thoroughly in those cases. The others have recovered completely.

“I think we’re actually pretty close to being ready to go to the FDA,” said Mitchell, who noted that he has no financial interest in the drug.

Mushroom experts, known as mycologists, are encouraged by the prospects of silibinin becoming available in the U.S., though they don’t necessarily believe it’s a certain cure -- or that all patients need the treatment.

“With good medical care now, 90 percent (of victims) will survive, with or without silibinin," said Michael Beug, chairman of the toxicology committee of the North American Mycological Association.

But Beug said that having the drug could help avoid the rush to extreme treatments, such as transplants.  

“To the extent that this slows down the doctor’s reach for a new liver, it’s a good thing,” he said.

The real question is, if Beug accidentally ate a death cap -- he says they’re known to be among the most delicious mushrooms in the world -- would he want the milk thistle drug and protocol?

“You bet,” he said.

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