Disclaimer: The opinions or assertions contained herein are the private views of the author, and are not to be construed as reflecting the Department of the Army, the Defense Threat Reduction Agency, or the Department of Defense.
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Research Commentary
U.S. Army Botulinum Neurotoxin (BoNT) Medical Therapeutics Research Program: past accomplishments and future directions†‡
Article first published online: 12 JUN 2009
DOI: 10.1002/ddr.20304
Published 2009 Wiley-Liss, Inc.
Issue
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Drug Development Research
Special Issue: Biodefense Countermeasure Development
Volume 70, Issue 4, pages 266–278, June 2009
Additional Information
How to Cite
Larsen, J. C. (2009), U.S. Army Botulinum Neurotoxin (BoNT) Medical Therapeutics Research Program: past accomplishments and future directions. Drug Development Research, 70: 266–278. doi: 10.1002/ddr.20304
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This article is a US Government work and, as such, is in the public domain in the United States of America.
Publication History
- Issue published online: 12 JUN 2009
- Article first published online: 12 JUN 2009
- Abstract
- References
- Cited By
Keywords:
- botulinum;
- therapeutics;
- Department of Defense
Abstract
The United States Army (USA) under the auspices of the Medical Research and Material Command (USAMRMC) and the Defense Threat Reduction Agency (DTRA) sponsored several major efforts to develop an effective medical countermeasure against botulinum neurotoxin (BoNT). This review focuses on the U.S. Army's research and development efforts for a BoNT therapeutic over the period from 1975–2007. Two antitoxin preparations: Human botulism immunoglobulin (BIG) and Botulism Immune Globulin F(ab')2 Heptavalent Equine (BIGHE) were administered to humans and shown to possess acceptable efficacy and safety levels. BIGHE was deployed in Operation Desert Storm/Desert Shield. BoNT/A monoclonal antibodies were developed and are currently undergoing clinical evaluation with funding from the National Institute of Allergy and Infectious Disease (NIAID). The development of small molecules for the treatment of BoNT has also been supported. Efforts have focused on molecules to inhibit nearly every aspect of BoNT pathogenesis. This would include toxin binding, translocation, catalytic activity, and recovery following intoxication. Several compounds capable of inhibiting toxin activity or mitigating the severity of paralysis have been identified. To date, none of the compounds possess the appropriate properties (safety, efficacy, solubility) to be considered for clinical studies. Drug Dev Res 70:266–278, 2009. Published 2009 Wiley-Liss, Inc.