In the 1980s, thousands of Iranians were killed from exposure to the nerve agents sarin and tobin unleased by Iraqi forces. Similar chemicals have been used against soldiers and civilians in recent wars and terrorist attacks. Now, researchers are reporting a new therapy that may be able to provide long-acting protection against these agents. Though the treatment has only been tested in rodents, some scientists say it could one day prevent lasting brain damage or death in people exposed to these deadly chemical weapons.
Nerve agents like sarin belong to a family of chemicals called organophosphates. Although some of these compounds are widely used in much lower concentrations as pesticides, the nerve agents are highly lethal because they get into the body quickly through the respiratory tract, eyes, or skin. Once inside cells, they inhibit an important enzyme whose normal function is to break down acetylcholine, a neurotransmitter that helps muscles contract. When too much acetylcholine builds up, victims experience violent muscle spasms and eventually stop breathing.
Current antidotes must be given as soon as possible, and although they can help mitigate the symptoms of poisoning, they don’t act directly on nerve agents. As a result, researchers have been trying to develop prophylactic “scavenging” molecules capable of seeking out and degrading nerve agents in the body upon exposure. But such “bioscavengers” have only been able to provide brief protection in various lab animals, and no such therapies have been approved by the U.S. Food and Drug Administration.
In the current study, researchers at the University of Washington in Seattle tried a new tack. They wrapped an organophosphate-targeting enzyme called OPH in a flexible polymer gel coating. The end result was nanometer-size particles capable of going undetected by the immune system and staying in the body longer than the enzyme alone. When given before exposure to nerve agents, the nanoparticles clear the chemicals from the bloodstream.
Rats given a single injection of the “nanoscavenger” were completely protected against organophosphate exposure for up to 5 days without side effects. In treated guinea pigs, the nanoscavenger protected animals from multiple sarin injections for 8 days, the team reports today in Science Translational Medicine.
The nanoscavenger could essentially act as a vaccine in people, says chemical engineer Shaoyi Jiang, a member of the team. If the therapy is optimized, the protection could potentially last for weeks or even months, he says.
Previous bioscavengers haven’t remained in the body long enough to confer protection, or they’ve sparked the body’s immune system to neutralize the antidote with antibodies, notes Jin Montclare, a protein engineer at New York University in New York City, who was not involved with the study. The new work appears to circumvent both of these concerns, she says.
Nerve agent nanoscavengers would be most practical for people who are at high risk of exposure to the chemical weapons, such as soldiers or first responders going into a contaminated area, says Janice Chambers, a toxicologist at Mississippi State University in Starkville who wasn’t involved in the work. But she says the therapy probably wouldn’t be useful for short-notice assaults such as terrorist attacks. “By the time you would be exposed and showing the signs of tremors or convulsions, it would be too late” to give the treatment.
The authors say the treatment could also help protect people working with certain pesticides. According to the World Health Organization, pesticides containing organophosphates cause 200,000 poisoning deaths per year in developing countries.
Next, the researchers plan to test how long the nanoscavenger works in monkeys, and they will also see whether multiple doses can be given. After that, a clinical trial would be needed to test the safety of the therapy in humans.