Chemical warfareEnzyme provides protection against nerve gas

Published 26 January 2011

Nerve agents disrupt the chemical messages sent between nerve and muscle cells, causing loss of muscle control, and ultimately leading to death by suffocation; protection against nerve gas attack is a significant component of the defense system of many countries around the world; nerve gases are used by armies and terrorist organizations, and constitute a threat to both the military and civilian populations, but existing drug solutions against them have limited efficiency; a multidisciplinary team of scientists at the Weizmann Institute of Science in Israel, succeeded in developing an enzyme that breaks down nerve agents efficiently before damage to nerves and muscles is caused

ASU professor Mor works on tobacco derivatives blocking nerve agents // Source: statepress.com

Protection against nerve gas attack is a significant component of the defense system of many countries around the world. Nerve gases are used by armies and terrorist organizations, and constitute a threat to both the military and civilian populations, but existing drug solutions against them have limited efficiency.

A multidisciplinary team of scientists at the Weizmann Institute of Science in Rehovot, Israel, succeeded in developing an enzyme that breaks down such organophosphorus nerve agents efficiently before damage to nerves and muscles is caused. Their results have recently been published in the journal Nature Chemical Biology. Recent experiments performed in a U.S. military laboratory (USAMRICD) have shown that injecting a relatively small amount of this enzyme into animals provides protection against certain types of nerve agents, for which current treatments show limited efficacy.

Nerve agents disrupt the chemical messages sent between nerve and muscle cells, causing loss of muscle control, and ultimately leading to death by suffocation. Nerve agents interfere with the activity of acetylcholinesterase, the enzyme responsible for the breakdown of the chemical messenger – acetylcholine. As a result, acetylcholine continues to exert its effect, resulting in constant muscle contraction throughout the body.

Several drugs exist that are used to treat cases of nerve agent poisoning. Although these drugs are somewhat effective when exposed to small doses of the nerve agent, they do not provide protection against high-dose exposure; they are not effective against all types of nerve agents; or they cause serious side effects. Neither are they able to prevent nor repair cerebral and motor nerve damage caused by the nerve agent.

An ideal solution to the problem is to use enzymes – proteins that speed up chemical reactions – to capture and break down the nerve agent before it gets the chance to bind to the acetylcholinesterase, thereby preventing damage. The main obstacle facing the realization of this idea, however, is that nerve agents are man-made materials and therefore, evolution has not developed natural enzymes that are able to carry out this task.

Scientists worldwide have previously succeeded in identifying enzymes that are able to break down similar materials, but these enzymes were characterized by low efficiency. Large amounts of the enzyme were therefore required in order to break down the nerve agent, rendering their use impractical.

This is where Professor Dan Tawfik of the Weizmann Institute’s Biological Chemistry Department enters the picture. Tawfik’s group developed a special method to artificially induce “natural