Doctors have long sought a “snakebite pill” that can deliver life-prolonging medicine when and where it’s most needed. Now experiments with an existing drug that treats heavy metal poisoning are stoking that dream.
Given orally, the drug saved or extended the lives of mice injected with lethal doses of viper venom, researchers report May 6 in Science Translational Medicine.
Snakebites kill tens of thousands of people every year, and leave many more with damaged limbs, in part due to difficulty getting quick, effective treatment (SN: 6/26/11). These bites often occur in remote locations, so many snakebite victims may have to travel hours or even days before reaching a medical facility equipped to provide lifesaving antivenom intravenously.
Nicholas Casewell, a biomedical scientist at the Liverpool School of Tropical Medicine in England, and his colleagues set out to find something portable and easy to administer that could counteract some of the most widespread and dangerous venom toxins: snake venom metalloproteinases. Often a major component in blood-poisoning venoms, like those of many vipers, these toxins cause a suite of issues, including massive internal hemorrhaging and tissue damage around the bite site.
The toxins, however, have an Achilles’ heel. “They rely on zinc ions to function,” Casewell says.
Drugs used to treat heavy metal poisoning bind up loose metal ions, so the researchers wondered if those drugs could also starve the toxins of zinc. One in particular — a compound called unithiol — did just that.
The researchers didn’t give the mice actual pills — the capsules were too large for the small animals to swallow. But oral administration of the liquid form of the drug 15 minutes after venom injection delayed the death of mice compared with mice that didn’t get the drug, and even boosted the survival of some mice. For example, of the five mice injected with West African carpet viper venom and given the drug, two lived and three lasted from 12 to 21 hours, while those that didn’t get the drug died within four hours.
Quickly administered oral unithiol worked as well as a delayed antivenom treatment — and even better when paired with it, the researchers found. Unithiol also prevented local tissue damage at the site of venom injection, suggesting that the drug could help prevent disabilities in addition to saving lives.
Researchers have wondered whether drugs that bind up metal ions could treat viper bites since the 1980s, says Leslie Boyer, a clinical researcher who studies envenomation treatment at the University of Arizona in Tucson. “This is an old drug, and it’s an old concept that’s finally being put to the test,” she says. But she stresses that results in mice aren’t the same as tests in humans.
If it does work in people, the treatment has potential “to buy those patients many hours before the onset of really serious symptoms,” Casewell says.
The team plans to run a safety trial in sub-Saharan Africa — one of the areas where viper bites exact a heavy toll — before giving the pill to actual snakebite victims. Previous trials of the drug before its use as a heavy metal poisoning treatment were conducted exclusively in white European men, so the safety trial is needed to reveal unforeseen side effects in an untested population, Casewell says.
Even if all goes well, Casewell notes that “this isn’t a single cure-all.” The treatment may do little, if anything, for bites from snakes such as cobras whose toxins predominantly target nerves instead of blood. Ultimately, he envisions pairing the pill with other drugs that inhibit more of the major toxins in snake venom, creating a universal snakebite pill.
That kind of accessible, first aid measure is “reasonable to expect … within the next few years,” Boyer says. But the next challenge will be to get the drug into the hands of those who need it most, who are often rural and poor, she says. “It won’t help at all to have a pill that minimizes the damage from snakebite if you don’t have the pill nearby.”