Botulinum Toxin: A Deadly Poison Sheds Its Negative Image (1996)

Editorials1 October 1996Botulinum Toxin: A Deadly Poison Sheds Its Negative ImageLance L. Simpson, PhDLance L. Simpson, PhDJefferson Medical College, Philadelphia, PA 19107Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-7-199610010-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Botulinum toxin is a remarkable substance. It is highly potent and can cause botulism, but it is also a highly efficacious medication that can produce clinical benefits in patients with nerve and muscle disorders. Interestingly, the underlying mechanism that causes disease is the same mechanism that provides clinical benefits.The major source of botulinum toxin is the organism Clostridium botulinum; C. barati and C. butyricum also produce the toxin [1-3]. The toxin is synthesized in seven serotypes, designated A, B, C, D, E, F, and G. Serotypes A, B, and E account for almost all cases of human botulism. Serotype ...References1. Simpson LL, ed. Botulinum Neurotoxin and Tetanus Toxin. San Diego: Academic Pr; 1989:1-422. Google Scholar2. Wellhoner HH. Tetanus and botulinum neurotoxins. In: Herken H, Hucho F, eds. Handbook of Experimental Pharmacology, vol. 102. Selective Neurotoxicity. Berlin: Springer-Verlag; 1992:357-417. Google Scholar3. Montecucco C, Schiavo G. Mechanism of action of tetanus and botulinum neurotoxins. Mol Microbiol. 1994; 13:1-8. Google Scholar4. DasGupta BR. Structure and biological activity of botulinum neurotoxin. J Physiol (Paris). 1990; 84:220-8. Google Scholar5. Woodruff BA, Griffin PM, McCroskey LM, Smart JF, Wainwright RB, Bryant RG, et al. Clinical and laboratory comparison of botulism from toxin types A, B, and E in the United States, 1975-1988. J Infect Dis. 1992; 166:1281-6. Google Scholar6. Townes JM, Cieslak PR, Hatheway CL, Solomon HM, Holloway JT, Baker MP, et al. An outbreak of type A botulism associated with a commercial cheese sauce. Ann Intern Med. 1996; 125:558-563. Google Scholar7. Arnon SS, Midura TF, Damus K, Wood RM, Chin J. Intestinal infection and toxin production by Clostridium botulinum as one cause of sudden infant death syndrome. Lancet. 1978; 1:1273-7. Google Scholar8. Arnon SS. Infant botulism. Annu Rev Med. 1980; 31:541-60. Google Scholar9. Chia JK, Clark JB, Ryan CA, Pollack M. Botulism in an adult associated with food-borne intestinal infection with Clostridium botulinum. N Engl J Med. 1986; 315:239-41. Google Scholar10. Sonnabend WF, Sonnabend OA, Grundler P, Ketz E. Intestinal toxicoinfection by Clostridium botulinum type F in an adult. Case associated with Guillain-Barre syndrome. Lancet. 1987; 1:357-61. Google Scholar11. Simpson LL. Molecular pharmacology of botulinum toxin and tetanus toxin. Annu Rev Pharmacol Toxicol. 1986; 26:427-53. Google Scholar12. Black JD, Dolly JO. Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. I. Ultrastructural autoradiographic localization and quantitation of distinct membrane acceptors for types A and B on motor nerves. J Cell Biol. 1986; 103:521-34. Google Scholar13. Black JD, Dolly JO. Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. II. Autoradiographic evidence for its uptake into motor nerves by acceptor-mediated endocytosis. J Cell Biol. 1986; 103:535-44. Google Scholar14. Simpson LL. Kinetic studies on the interaction between botulinum toxin type A and the cholinergic neuromuscular junction. J Pharmacol Exp Ther. 1980; 212:16-21. Google Scholar15. Simpson LL. Ammonium chloride and methylamine hydrochloride antagonize clostridial neurotoxins. J Pharmacol Exp Ther. 1983; 225:546-52. Google Scholar16. Simpson LL, Coffield JA, Bakry N. Inhibition of vacuolar adenosine triphosphatase antagonizes the effects of clostridial neurotoxins but not phospholipase A2 neurotoxins. J Pharmacol Exp Ther. 1994; 269:256-62. Google Scholar17. Schiavo G, Rossetto O, Benfenati F, Poulain B, Montecucco C. Tetanus and botulinum neurotoxins are zinc proteases specific for components of the neuroexocytosis apparatus. Ann N Y Acad Sci. 1994; 710:65-75. Google Scholar18. Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med. 1991; 324:1186-94. Google Scholar19. Jankovic J. Botulinum toxin in movement disorders [Review]. Curr Opin Neurol. 1994; 7:358-66. Google Scholar20. Jankovic J, Hallet M, eds. Therapy with Botulinum Toxin. New York: Marcel Dekker; 1994. Google Scholar Author, Article, and Disclosure InformationAffiliations: Jefferson Medical College, Philadelphia, PA 19107Grant Support: In part by National Institutes of Health grant NS-22153 and by Department of the Army contract DAMD17-90-C-0048.Corresponding Author: Lance L. Simpson, PhD, Departments of Medicine and Pharmacology, Jefferson Medical College, 1020 Locust Street, Philadelphia, PA 19107. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAn Outbreak of Type A Botulism Associated with a Commercial Cheese Sauce John M. Townes , Paul R. Cieslak , Charles L. Hatheway , Haim M. Solomon , J. Ted Holloway , Michael P. Baker , Charles F. Keller , Loretta M. McCroskey , and Patricia M. 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