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Prophylaxis and Therapy Against Chemical Agents (Prophylaxie Et Thérapie Contre Les Agents Chimiques)

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Prophylaxis and Therapy Against Chemical Agents (Prophylaxie Et Thérapie Contre Les Agents Chimiques) NORTH ATLANTIC TREATY RESEARCH AND TECHNOLOGY ORGANISATION ORGANISATION AC/323(HFM-041)TP/280 www.rto.nato.int RTO TECHNICAL REPORT TR-HFM-041 Prophylaxis and Therapy Against Chemical Agents (Prophylaxie et thérapie contre les agents chimiques) Final Report of the HFM-041/TG-004 for the Period 1999 to 2005. Published November 2009 Distribution and Availability on Back Cover NORTH ATLANTIC TREATY RESEARCH AND TECHNOLOGY ORGANISATION ORGANISATION AC/323(HFM-041)TP/280 www.rto.nato.int RTO TECHNICAL REPORT TR-HFM-041 Prophylaxis and Therapy Against Chemical Agents (Prophylaxie et thérapie contre les agents chimiques) Final Report of the HFM-041/TG-004 for the Period 1999 to 2005. The final report of the HFM-041 includes the complete scientific proceedings of meetings sponsored under this task group and held in 1999, 2000, 2002, 2003 and 2005. The report also includes a summary report on bioscavengers as a new pre-treatment for nerve agent poisoning. The Research and Technology Organisation (RTO) of NATO RTO is the single focus in NATO for Defence Research and Technology activities. Its mission is to conduct and promote co-operative research and information exchange. The objective is to support the development and effective use of national defence research and technology and to meet the military needs of the Alliance, to maintain a technological lead, and to provide advice to NATO and national decision makers. The RTO performs its mission with the support of an extensive network of national experts. It also ensures effective co-ordination with other NATO bodies involved in R&T activities. RTO reports both to the Military Committee of NATO and to the Conference of National Armament Directors. It comprises a Research and Technology Board (RTB) as the highest level of national representation and the Research and Technology Agency (RTA), a dedicated staff with its headquarters in Neuilly, near Paris, France. In order to facilitate contacts with the military users and other NATO activities, a small part of the RTA staff is located in NATO Headquarters in Brussels. The Brussels staff also co-ordinates RTO’s co-operation with nations in Middle and Eastern Europe, to which RTO attaches particular importance especially as working together in the field of research is one of the more promising areas of co-operation. The total spectrum of R&T activities is covered by the following 7 bodies: • AVT Applied Vehicle Technology Panel • HFM Human Factors and Medicine Panel • IST Information Systems Technology Panel • NMSG NATO Modelling and Simulation Group • SAS System Analysis and Studies Panel • SCI Systems Concepts and Integration Panel • SET Sensors and Electronics Technology Panel These bodies are made up of national representatives as well as generally recognised ‘world class’ scientists. They also provide a communication link to military users and other NATO bodies. RTO’s scientific and technological work is carried out by Technical Teams, created for specific activities and with a specific duration. Such Technical Teams can organise workshops, symposia, field trials, lecture series and training courses. An important function of these Technical Teams is to ensure the continuity of the expert networks. RTO builds upon earlier co-operation in defence research and technology as set-up under the Advisory Group for Aerospace Research and Development (AGARD) and the Defence Research Group (DRG). AGARD and the DRG share common roots in that they were both established at the initiative of Dr Theodore von Kármán, a leading aerospace scientist, who early on recognised the importance of scientific support for the Allied Armed Forces. RTO is capitalising on these common roots in order to provide the Alliance and the NATO nations with a strong scientific and technological basis that will guarantee a solid base for the future. The content of this publication has been reproduced directly from material supplied by RTO or the authors. Published November 2009 Copyright © RTO/NATO 2009 All Rights Reserved ISBN 978-92-837-0092-0 Single copies of this publication or of a part of it may be made for individual use only. The approval of the RTA Information Management Systems Branch is required for more than one copy to be made or an extract included in another publication. Requests to do so should be sent to the address on the back cover. ii RTO-TR-HFM-041 Table of Contents Page List of Figures/Tables v Membership of Task Group – Prophylaxis and Therapy Against Chemical Agents vi HFM-041/TG-004 Executive Summary and Synthèse ES-1 Chapter 1 – Summary of the Meeting held in Brussels (BEL) 22-26 March 1999 1-1 1.1 Cooperation 1-2 Chapter 2 – Summary of the Meeting held in The Hague (NLD) 1-5 October 2000 2-1 2.1 Cooperation 2-2 Chapter 3 – Summary of the Meeting held in Oslo (NOR) 4-7 November 2002 3-1 3.1 Cooperation 3-1 Chapter 4 – Summary of the Meeting held in Medicine Hat (CAN) 29 September – 4-1 3 October 2003 4.1 Cooperation 4-2 Chapter 5 – Summary of the Meeting held in Hradec Králové (CZE) 23-26 May 5-1 2005 5.1 Cooperation 5-2 Chapter 6 – Summary of Accomplishments 6-1 Chapter 7 – Terms of Reference 7-1 Annex A – Task Group on Prophylaxis and Therapy Against Chemical Agents A-1 A.1 Meeting of TG-004 – 22-26 March 1999, Brussels, Belgium A-1 A.1.1 Program A-1 A.2 Meeting of TG-004 – 1-5 October 2000, The Hague, Netherlands A-7 A.2.1 Program A-7 A.3 Meeting of TG-004 – 4-7 November 2002, Oslo, Norway A-11 A.3.1 Program A-11 A.3.2 Posters A-17 RTO-TR-HFM-041 iii A.4 Meeting of TG-004 – 29 September – 3 October 2003, Medicine Hat, Alberta, Canada A-19 A.4.1 Program A-19 A.4.2 Posters A-21 A.5 Meeting of TG-004 – 23-26 May 2005, Hradec Králové, Czech Republic A-24 A.5.1 Program A-24 A.5.2 Posters A-29 Annex B – Nerve Agent Bioscavengers: Progress in Development of a New Mode B-1 of Protection Against Organophosphorus Exposure Abstract B-1 B.1 Introduction B-2 B.2 Current Therapy for Nerve Agent Exposure B-2 B.3 Nerve Agent Bioscavengers: An Alternative to Conventional Approaches B-3 B.4 Stoichiometric Scavengers and the Protection they Offer B-5 B.4.1 Antibodies B-5 B.4.2 Enzymes B-6 B.5 Catalytic Bioscavengers B-11 B.6 Behavioral Effects B-17 B.7 Behavioral Effects of Scavengers Alone B-17 B.8 Summary B-19 B.9 References B-20 Annex C – Complete Scientific Programs for the TG-004 Meetings held from C-1 1999 – 2005 iv RTO-TR-HFM-041 List of Figures/Tables Figure Page Figure B-1 Biochemical Basis for CaE Cellular Trafficking B-9 Figure B-2 Effect of Plasma CaE Concentration on Soman LD50 (administered subcutaneously) B-9 in Different Species Figure B-3 Comparative Reactivation Kinetics of Soman-Inhibited Human B-14 Butyrylcholinesterase Single Mutant G117H (ϒ) and Double Mutant G117H/E197Q (●) Figure B-4 A Ball and Stick Computer Model of the Active Site of the Double Mutant of B-15 Butyrylcholinesterase G117H/E197Q Table Table B-1 Protection from Organophosphorus Intoxication by Antibody Bioscavengers B-5 Table B-2 Protection from Organophosphorus Intoxication by the Bioscavenger FBS-AChE B-6 Table B-3 Protection from Organophosphorus Intoxication by the Bioscavenger eq-BuChE B-7 Table B-4 Protection from Organophosphorus Intoxication by Endogenous Plasma CaE B-8 Table B-5 Protection from Organophosphorus Intoxication by HuBuChE Bioscavengers B-11 Table B-6 Kinetic Properties of Naturally Occurring Catalytic Bioscavengers B-12 Table B-7 Kinetic Properties of Catalytic Mutated BuChE Bioscavengers B-16 Table B-8 Kinetic Properties of Mouse Derived Catalytic Antibody Bioscavengers B-17 Table B-9 Extent of Behavioral Deficits Following Bioscavenger Administration or B-18 Conventional Therapy RTO-TR-HFM-041 v Membership of Task Group – Prophylaxis and Therapy Against Chemical Agents HFM-041/TG-004 CHAIRMAN Dr. David LENZ Research Division US Army Medical Research Institute of Chemical Defense 3100 Ricketts Point Rd. Aberdeen Proving Ground, MD 21010-5400 UNITED STATES† e-mail: [email protected] CANADA NETHERLANDS Dr. Thomas SAWYER Dr. Herman VAN HELDEN DRDC Suffield Pulmonary and CNS Pharmacology Chemical Biological Defence Section TNO Defence, Security and Safety PO Box 4000 Research Group Diagnosis and Therapy Medicine Hat, Alberta T1A 8K6 PO Box 45 e-mail: [email protected] 2280 AA Rijswijk e-mail: [email protected] CZECH REPUBLIC Dr. Josef FUSEK NORWAY Vice Dean for Research, University of Defence Prof. Dr. Pål AAS Faculty of Military Health Sciences Norwegian Defence Research Establishment Department of Toxicology Division for Protection and Materiel Trebesska 1575 Postbox 25 – Instituttveien 20 500 01 Hradec Kralove NO-2027 Kjeller e-mail: [email protected] e-mail: [email protected] FRANCE* SWEDEN Dr. Patrick MASSON Dr. Gudrun CASSEL Service de Santé des Armées FOI CBRN Defence and Security 24 Avenue des Maquis du Grésivaudan Cementvägen 20 BP 87 S-90182 Umeå 38702 La Tronche Cedex e-mail: [email protected] e-mail: [email protected] UNITED KINGDOM * GERMANY Dr. Paul RICE Dr. Ladislaus SZINIZC Dstl Porton Down Institute of Pharmacology and Toxicology Salisbury, Wiltshire SP4 0JQ German Armed Forces Medical Academy e-mail: [email protected] Neuherbergstrasse 11 80937 Munich e-mail: [email protected] vi RTO-TR-HFM-041 *Current Points of Contact FRANCE GERMANY Dr. Fredric DORANDEU Dr. Horst THIERMANN Institut de Recherche Biomédicale des Armées Institute of Pharmacology and Toxicology 24 avenue des Maquis du Grésivaudan German Armed Forces Medical Academy 38702 La Tronche Cedex Neuherbergstrasse 11 e-mail: [email protected] 80937 Munich e-mail: [email protected] †Alternate Point of Contact UNITED STATES Dr.
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