Enzyme key to chemical weapon weakness
Vulnerable mice help explain nerve-gas action.
nature.com
17 March 2003
HELEN R. PILCHER
The delayed effects of nerve poisons used in chemical warfare depend on a key molecule, new research with mice shows(1).
The same mechanism in humans could mean that some people are genetically more susceptible to the delayed effects of nerve agents.
"You only need a low level of the toxin to get the effects," says biologist Carolee Barlow from the Salk Institute in La Jolla, California. Understanding how the nerve agents work could help researchers to develop new antidotes.
Nerve agents called organophosphates cause the delayed poisoning. Organophosphate weapons such as sarin and VX are thought to have been used in Iraq during the Gulf War. Their latent effects have been implicated as a cause of the mysterious and controversial Gulf War syndrome suffered by veterans of the 1991 conflict.
Organophosphates are more commonly used as pesticides, so they often cause accidental poisoning. Within hours of exposure to high doses of organophosphates, victims suffer seizures and paralysis, after which breathing stops. Without medical intervention, most victims die.
About a week later, survivors go on to develop a second wave of symptoms: the result of the chemical destroying nerves, causing severe and irreversible paralysis.
Now Barlow's team find that mice with low levels of an enzyme called NTE are more sensitive to the effects of organophosphates. They were less mobile, had seizures and were twice as likely to die than normal animals.
What NTE does is far from clear, explains team member Christopher Winrow. But organophosphates may block its activity, causing the longer-term paralytic effects.
Humans also have a gene for NTE, suggesting we also have the same enzyme. If so, drugs to boost NTE levels might be used in advance of a nerve-gas attack, Winrow speculates.
In the short-term, however, the team's vulnerable mice should prove to be a valuable research tool. So far, chickens, which succumb to pesticide poisoning easily, have been used to study poisoning. But parallels between us and mice, our fellow mammals, are easier to draw.
Although more than 30,000 human cases of organophosphate-related paralysis have been studied, "there is no cure other than to avoid exposure", says David Ray, a toxicologist at the University of Nottingham, UK.
References
(1) Winrow, C.J. et al . Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity. Nature Genetics , published online, doi:10.1038/ng1131 (2003).
© Nature News Service / Macmillan Magazines Ltd 2003 |
