Human Enzyme Made in Plants May Protect Against Nerve Agents

On Monday March 20, 1995, 5 members of the Japanese cult, Aum Shinrikyo walked onto their appointed trains with deadly parcels of the nerve agent Sarin wrapped in plastic bags and newspapers. At prearranged stations, the sarin packets were dropped and stabbed with umbrella tips to release deadly sarin vapours. Twelve people were killed, and nearly 5,000 were hospitalized.

As a result of the rise in global terrorism such chilling attacks remain a distinct possibility. However, the means to fully treat patients remains elusive as current anti-nerve agent treatments can only help symptoms but do not prevent long term nerve damage.

The human nervous system is constantly chattering away with the firing of impulses along lines of interconnected nerve cells. Signals are sent from the brain to various parts of the body through firing of impulses from one nerve cell to the next, and also from nerve to muscle cells which then results in a muscle contraction, for example contraction of muscles associated with breathing. Transmission of impulses from nerve to muscle cells requires the release of a substance called acetycholine at the end of the nerve cell which is immediately broken down by acetycholinesterase (AChE) into inactive components. The immediate breakdown of AChE is essential for coordinated movement of muscles. If this does not occur, acetycholine floods the nervous system resulting in paralysis and disorganized muscle contractions eventually leading to death when muscles required for breathing and heart muscles are affected. This occurs with nerve agents which prevent the breakdown of AChE.

Butyrylcholinesterase (BChE) occurs in blood, scavenging and binding to toxic nerve agents, such as sarin gas to prevent them from doing their dirty work of stopping the breakdown of AChE. However, there is not enough of BChE within the blood for it to be mass produced for stockpiling for the next bioterrorism attack, and of course there is the risk of transmitting blood disease- think back to the haemophilia scare of the 1980s when contamined blood products resulted in patients being needlessly infected with HIV.

However, recent research by Brian Geyer and colleagues in the November issue of The Proceedings of the National Academy of Sciences suggests an alternative for mass production of BChE to treat nerve agent attacks. They used tobacco plants which were genetically modified, also known as transgenic plants, to over produce BChE in their leaves. In their experiments Geyer et al. showed that this plant-derived BChE protected lab animals exposed to nerve agents and alleviated symptoms of poisoning such as difficulties in breathing and convulsions, and also prevented death. They also found that they could make the enzyme persist in the blood of the lab animals for longer by binding it to the chemical polyethylene glycol (PEG) to allow for further protection.

Much work remains before plant-derived BChE can be used to protect humans against nerve agents, but the fact that it can be produced in plants and demonstrates promising signs of benefit in lab animals is tantalizing.

As transgenic plants could be an abundant and relatively inexpensive source of BChE, they could be used for large-scale production and stockpiling of this treatment for the likely event of another terrorism attack.

Reference: http://www.pnas.org/content/early/2010/11/05/1009021107

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