New treatment could combat deadly chemical agents

An enzyme treatment which could neutralise the effects of lethal chemicals responsible for the deaths of hundreds of thousands of people across the world has been developed by experts at the University of Sheffield.

Organophosphorus agents (OP) are used as pesticides in developing countries and acute poisoning is common because of insufficient control, poor storage, ready availability, and inadequate education amongst farmers.

It is estimated about 200,000 people die each year across the world from OP poisoning, through occupational exposure, unintentional use and misuse, mostly in developing countries like India, Pakistan, and Sri Lanka and through deliberate terrorist activities.

OPs include compounds like Tabun, which was developed in 1936 by German scientists during World War II, Sarin, Soman, Cyclosarin, VX, and VR.

Using a modified human enzyme, scientist Professor Mike Blackburn from the University of Sheffield’s Department of Molecular Biology and Biotechnology collaborated in a consultancy role with Professor Alexander Gabibov of the Shemyakin-Ovchinnikov Institute, Moscow, and Professor Patrick Masson of the Département de Toxicologie, Centre de Recherches du Service de Santé des Armées, to create a “bioscavenger” which was found to protect mice against the nerve agent VR and showed no lasting effects.

In studies performed at the Institute of Bioorganic Chemistry in Pushchino, Russia, a total of eight mice were treated with the new enzyme after being subjected to enough of the VR agent to kill several of the animals – about 63 mg per kg – and all survived.

Professor Blackburn said: “This current publication describes a novel method to generate a bioscavenger for the Russian VR organophosphorus agent with the key property of being long-acting in the bloodstream.

“That has been achieved by a combination of chemical surface modification (polysialylation) and biotechnology of production (through the use of an in vitro CHO-based expression system employing genes encoding butyrylcholinesterase and a proline-rich peptide under special promoter control).

The research has been published in the journal PNAS.

Additional information To view the paper online visit: http://www.pnas.org/cgi/doi/10.1073/pnas.1211118110 The University of Sheffield With nearly 25,000 students from 125 countries, the University of Sheffield is one of the UK’s leading and largest universities. A member of the Russell Group, it has a reputation for world-class teaching and research excellence across a wide range of disciplines. The University of Sheffield was named University of the Year in the Times Higher Education Awards 2011 for its exceptional performance in research, teaching, access and business performance. In addition, the University has won four Queen’s Anniversary Prizes (1998, 2000, 2002, and 2007). These prestigious awards recognise outstanding contributions by universities and colleges to the United Kingdom’s intellectual, economic, cultural and social life. Sheffield also boasts five Nobel Prize winners among former staff and students and many of its alumni have gone on to hold positions of great responsibility and influence around the world. The University’s research partners and clients include Boeing, Rolls-Royce, Unilever, Boots, AstraZeneca, GSK, ICI, Slazenger, and many more household names, as well as UK and overseas government agencies and charitable foundations. The University has well-established partnerships with a number of universities and major corporations, both in the UK and abroad. Its partnership with Leeds and York Universities in the White Rose Consortium has a combined research power greater than that of either Oxford or Cambridge.