Venomous snakes kill thousands every year. A California doctor may have a solution

John Heenan knew the horror of feeling a sting on his leg, then looked down and saw two bright red puncture wounds about an inch apart and a large rattlesnake. running through the tall grass.

It was a summer morning in 2017, and the 74-year-old horticulturist was carrying a box of fruit to a Marin County orchard when, he said, I stepped on him, then called a colleague, Hey , I was bitten. by a rattlesnake.

It’s a snapshot imprinted on Heenan’s brain. The fangs hit a nerve, and I felt the venom moving through my system, he recalled, shuddering at the memory. I began to gasp, and struggled to breathe as if the air was running out of me.

Heenan was rushed to the hospital, where he was in a coma for the next four days. During that time, he was given 28 vials of antivenom intravenously at a cost of $3,400 per vial.

When he regained consciousness, there were two people at his bedside, his wife and expedition doctor Matthew Lewin, who smiled and said, You are a lucky man.

Matthew Lewin, left, and John Heenan stand in the orchard where Heenan was bitten by a 5 1/2-foot-long Pacific rattlesnake. The horticulturist at the College of Marin’s Indian Valley Campus was in a coma for four days. (Louis Sahagun/Los Angeles Times)

Heenan learned that Lewin was hot on the trail of a new treatment for the long-term, painful and often fatal effects of venomous snakebites: It was a pill that he said was intended to buy victim enough time to go to the hospital.

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Snake venom is a complex cocktail of toxins, amino acids and proteins that primarily evolved to immobilize and kill prey, but it also prepares tissues for digestion. In humans, the toxin causes severe inflammation and blood pressure instability, neuromuscular weakness and paralysis, hemorrhage, and skeletal muscle death, leading to permanent tissue loss and amputation.

The World Health Organization estimates that 138,000 people are killed by poisonous snakes every year, and most of them die before they can reach emergency medical care. This suffering continues with little anger or publicity because snakebites often occur in poor, backwater areas, and there is no easy way to treat snakebites in the field.

Nature provides an abundance of aggressive predators to watch out for: rattlesnakes, copperheads, water moccasins and coral snakes in the United States; kraits of Southeast Asia; taipans in Australia; Nikolskys snake in Ukraine; Gaboon viper with 2-inch-long fangs in Africa; and bushmasters of Central America. Then there are Russels snakes, large, angry snakes that are responsible for 25,000 deaths in India every year.

Common standard-of-care antivenoms are very expensive, require refrigeration and must be administered intravenously in a hospital setting. They are also species specific, which means that choosing the right antibiotic requires knowing what kind of snake bit you.

As a result, rattlesnake bite survivors in Southern California, for example, will receive a second painful surprise when presented with hospital bills totaling hundreds of thousands of dollars.

Lewin has been working for a decade to develop an easy to use, needle-free solution to all drug problems called Varespladib.

What makes Varespladib so promising is that it blocks phospholipase-A2, a highly toxic protein that is present in 95% of all snake venoms and plays a direct role in life-threatening tissue destruction, catastrophic bleeding, paralysis and respiratory failure. Proponents say the small synthetic molecule has the potential to halt or reverse neurological damage, as well as restore the blood’s normal clotting ability if administered soon after envenoming. .

Drug tests were conducted by Ophirex Inc. a public benefit corporation founded by Lewin with musician and businessman Jerry Harrison in Corte Madera, Calif.

The US Food and Drug Administration a year ago gave Varespladib fast track designation to accelerate the development and review of its safety and effectiveness, as well as Ophirex’s proposals for the manufacture and distribution of medicine.

The Department of Defense also invested about $24 million in the effort, saying the drug could provide an important capability to special forces teams deployed in extreme conditions where snakebites are a significant threat. of life and limb.

“Ophirex may help us extend the window of time needed for evacuation in the event of a snake bite, said Lindsey Garver, deputy manager for the Army Medical Materiel Agency Warfighter Protection and Acute Care Project. There is also a psychological that’s the benefit of having something in your pocket that can save a life.

But getting any new drug from the laboratory to the market is an expensive, painstaking process that sometimes takes months to show promise but years to perfect.

The company is completing a Phase II clinical trial in the United States and India to determine the tolerability and potential side effects of the multi-dose drug regimen in about 100 suspected or confirmed snakebite victims. Among them is a person who a month ago was bitten by a sidewinder rattlesnake near the desert resort city of Palm Springs.

A federal analysis of the results is expected next year and will ultimately determine whether Ophirex has a blockbuster snake venom treatment with military and global market opportunities.

I definitely underestimated the amazing complexity of a task like this, said Lewin, 55, expedition doctor for the California Academy of Sciences in San Francisco. Its low.

The company has assembled an impressive board of directors: Derrick Rossi, a stem cell scientist and co-founder of Moderna; Curt LaBelle, chair of Global Health Funds; Tim Garnett, former chief medical officer for Eli Lilly and Co.; and Hans Bishop, co-founder of Altos Labs Inc., a biotechnology research company.

Our company is trying to create a cure for a neglected global crisis, says Rossi. The majority of people killed or maimed by snake bites are village farmers and children who work in the fields without shoes.

Varespladib was originally discovered and developed by Eli Lilly and Co. to prevent inflammation. The company abandoned that effort, however, after clinical studies failed to produce the desired results.

Since then, the drug’s molecular patents have expired, giving Ophirex an opportunity for us to build an appropriate patent portfolio, said Nancy Koch, chief executive of Ophirex.

The proposed price tag of the tablet remains unclear. We haven’t made any price estimates yet, Koch said. But we want to make medicine accessible worldwide, and to make that possible we are studying ways to reduce manufacturing costs.

To hear Lewin speak, Ophirex emerges from a terrible event. In 2001, Joseph Slowinski, a herpetologist at the California Academy of Sciences in San Francisco, died 30 hours after he was bitten by a small venomous snake in the mountain forest of northern Myanmar.

No antivenom was available in the remote area, a five-day trek from the nearest town. Heroic efforts to save him were unsuccessful.

A decade later, after a trip to the same region, Lewin, director of the academy’s Center for Exploration and Travel Health, began to ponder the possibility of a needle-free treatment that could be administered in the field immediately. immediately after being bitten.

Lewin initially set his sights on proving that the potentially fatal paralytic effects of certain toxic substances could be reversed by an antiparalytic drug administered by nasal spray.

With that goal in mind, Lewin volunteered to be a test subject.

In a 2013 experiment conducted with a team of anesthesiologists at a UC San Francisco research laboratory, Lewin allowed himself to be paralyzed by curare, a chemical that is usually administered intravenously as a paralyzing agent for surgical procedures.

A few moments later, he said, I could not speak, felt dizzy and had trouble breathing.

The team then administered a nasal spray, and within 20 minutes Lewin was on the mend. The results of the experiment were published online in the medical journal Clinical Case Reports.

It was horrible, and I will never do that again, Lewin said. But the experiment proved that the paralysis could be reversed without intravenous drugs.

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Lewins’ career arc has taken him from emergency rooms to wilderness medicine as a physician on scientific expeditions sponsored by the American Museum of Natural History, the Kellogg Foundation and National Geographic.

Not all of his research takes place in remote corners of the world, however. Studying the factors that influence the severity of snake bites means working with scientists like William Hayes, a professor at Loma Linda University School of Medicine in Loma Linda, Calif., who keeps a variety of snake venom available for laboratory refrigerator testing.

It also means studying the physical and financial struggles of survivors like John Heenan, whose hospital bills rose to more than $350,000 after he was bitten at the College of Marin’s Indian Valley Campus.

Medicare eventually covered my medical expenses, but I had to pay about 300 bucks for the ambulance service, Heenan said, shaking his head.

The college, for its part, later posted a large digital welcome sign at its entrance that read: “BEWARE: Enter Rattlesnake Country. Walk alert.

Heenan wouldn’t argue with any of that. But he also had high hopes for Lewin’s vision.

Everyone should carry some of the pills in their first aid kits and lunch boxes,” he said. “Of course, they should also watch where they walk.”

This story originally appeared in the Los Angeles Times.

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