John Heenan knew the horror of a sting on his foot, then looked down to see two bright red stab wounds an inch apart as a giant rattlesnake slithered into the tall grass.
It was a morning in the summer of 2017, and the 74-year-old horticulturist was carrying a box of fruit in a Marin County orchard. He said, “I stepped right on him,” and then yelled to his partner, “Hey, I’ve been bitten by a rattlesnake.” .
This is a snapshot that is etched in Heenan’s mind. The fangs hit a vein and I could feel the venom coursing through my entire system, he recalled. I started convulsing and breathing hard, as if the wind had been blown away.
Heenan was rushed to hospital, where he remained in a coma for the next four days. During this period, he received 28 intravenous vials of antivenom, each costing $3,400.
When he regained consciousness, there were two people at his bedside, his wife and expedition doctor Matthew Lewin, who smiled and said, “You’re a lucky man.”
Heenan later learned that Lewin was actively seeking a new treatment for the long-term, painful and even fatal effects of venomous snake bites: the pill, he said, was intended to at least provide victims with enough Time to go to the hospital.
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Snake venom is a complex mixture of toxins, amino acids, and proteins that evolved primarily to immobilize and kill prey, but it also primes it for digestion. In humans, the venom causes severe swelling 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 venomous snakes each year, most of whom die before emergency medical care is available. The painful occurrences rarely generate public outrage or publicity because snakebites occur most often in poor, backward areas and there are no easy ways to treat snakebites in the wild.
Nature provides plenty of slithering attackers to be wary of: rattlesnakes, copperheads, sambars, and coral snakes in the United States; kraits in Southeast Asia; taipan in Australia; Nikolsky vipers in Ukraine; and Gabonese vipers in Africa. , with tusks up to 2 inches long; and the jungle master of Central America. There’s also the Russell’s viper, a large, ill-tempered snake that kills 25,000 people in India every year.
Typical standard-of-care antivenoms are expensive, require refrigeration, and must be administered intravenously in a hospital setting. They’re also species-specific, which means choosing the right antivenom requires knowing what type of snake bit you.
For example, rattlesnake bite survivors in Southern California were in for a second painful surprise when they received 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 of these problems: a drug called Varespladib.
The promise of Varespladib lies in its ability to block phospholipase A2, a highly toxic protein found in 95% of snake venoms that plays a direct role in life-threatening tissue destruction, catastrophic hemorrhage, paralysis and respiratory failure. effect. Proponents say the synthetic small molecule has the potential to stop or reverse nerve damage and restore normal blood clotting when taken immediately after poisoning.
The drug is being tested at Ophirex Inc., a public benefit corporation Lewin founded in Corte Madera, Calif., with musician and entrepreneur Jerry Harrison.
The U.S. Food and Drug Administration granted Varespladib Fast Track designation a year ago to expedite the development and review of its safety and effectiveness, as well as Ophirex’s recommendation to manufacture and distribute the drug.
The Department of Defense, which has also invested about $24 million, said the drug could provide vital capabilities to special forces deployed in austere conditions where snake bites pose a significant threat to life and limb.
“Ophirex can help us extend the time it takes to evacuate in the event of a snake bite,” said Lindsey Garver, deputy manager of Warrior Protection and Emergency Care Programs at the Army Medical Materiel Agency. “The life-saving pocket.”
But getting any new drug from the lab to the market is an expensive and complex process that sometimes can take just 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 a multiple-dose regimen of the drug in about 100 patients with suspected or confirmed snake bites. One of the men was bitten by a rattlesnake a month ago near the desert resort city of Palm Springs.
A federal analysis of the results is expected sometime next year and will ultimately determine whether Ophirex has a blockbuster snakebite treatment with military and global market opportunities.
“I certainly underestimated the staggering complexity of a mission like this,” said Lewin, 55, an expedition doctor at the California Academy of Sciences in San Francisco. Humbling.
The company has assembled an impressive board of directors: Derrick Rossi, a stem cell scientist and Moderna co-founder; Curt LaBelle, chairman of the Global Health Fund; Tim Garnett, former chief medical officer of Eli Lilly and Company; Hans Bishop Hans Bishop is the co-founder of Altos Labs Inc., a biotechnology research company.
“Our company is trying to produce a drug to address a neglected global crisis,” Rossi said. The vast majority of people killed or maimed by snake bites are farmers and children working barefoot in the fields.
Varespladib was originally discovered and developed by Eli Lilly and Company to suppress inflammation. However, the company abandoned the effort after clinical studies failed to produce expected results.
Ophirex CEO Nancy Koch said, “Since then, the patent on the drug molecule has expired, which provides Ophirex with the opportunity to build an appropriate patent portfolio.”
The price of the proposed drug remains unclear. “We haven’t made any estimates on pricing yet,” Koch said. But we want to make this drug available around the world, and to achieve that we are looking at ways to reduce manufacturing costs.
According to Lewin, Ophirex emerged from a tragedy. In 2001, Joseph Slowinski, a herpetologist at the California Academy of Sciences in San Francisco, died 30 hours after being bitten by a small venomous snake in the mountainous jungles of northern Myanmar.
Antivenom is not available at this remote site, which is a five-day hike from the nearest town. Heroic efforts to save him were unsuccessful.
Ten years later, after a trip to the same area, Lewin, director of the college’s Discovery and Travel Health Center, began thinking about whether needle-free treatment could be done on-site immediately after a bite.
Lewin’s initial goal was to demonstrate that the potentially fatal paralyzing effects of certain toxic substances could be reversed by an anti-paralytic drug administered as a nasal spray.
With this goal in mind, Lewin volunteered to become a test subject.
In a 2013 experiment conducted by a team of anesthesiologists at a UCSF research lab, Lewin allowed himself to be paralyzed with a derivative of curare, a chemical commonly injected intravenously as a paralyzing agent during surgery. substance.
After a while, he said, I couldn’t speak, felt dizzy and had trouble breathing.
The team then administered a nasal spray and Lewin recovered within 20 minutes. The experimental results have been published online in the medical journal “Clinical Case Reports”.
“It was horrible and I would never do it again,” Lewin said. But experiments have shown that paralysis can be reversed without the need for intravenous drugs. “
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Louis’ career took him from the emergency room to wilderness medicine as a physician on scientific expeditions sponsored by the American Museum of Natural History, the Kellogg Foundation, and National Geographic.
However, not all of his research took place in remote corners of the world. Studying the factors that influence snake bite severity requires collaboration with scientists such as William Hayes, a professor at Loma Linda University School of Medicine in Loma Linda, Calif., who keeps a variety of snake venoms in a lab refrigerator for testing.
It also means studying the physical and financial plight of survivors like John Heenan, whose hospital bills soared to more than $350,000 after he was bitten at the College of Marin’s Indian Valley campus.
Health insurance eventually paid for my medical treatment, but I had to pay about $300 for ambulance service, Heenan said, shaking her head.
For its part, the college later placed a large digital welcome sign at its entrance that read: “Attention: Entering rattlesnake country. Be alert when walking.”
Heenan wouldn’t dispute that. But he also has high hopes for Lewin’s vision.
Everyone should carry some of these tablets in their first aid kit and lunch box. “He said. “Of course, they should also watch their step.”
This story originally appeared in the Los Angeles Times.
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