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Chapter 3 - Pharmacology of Botulinum Toxin Therapy

Published online by Cambridge University Press:  02 November 2023

By
Daniel Truong ,
Frank Xing  and
Mark Hallett
Edited by
Daniel Truong ,
Dirk Dressler ,
Mark Hallett ,
Christopher Zachary  and
Mayank Pathak
Daniel Truong
Affiliation:
University of California, Riverside
Dirk Dressler
Affiliation:
Hannover Medical School
Mark Hallett
Affiliation:
National Institutes of Health (NIH)
Christopher Zachary
Affiliation:
University of California, Irvine
Mayank Pathak
Affiliation:
Truong Neuroscience Institute
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Summary

Botulinum neurotoxins (BoNTs) are protins derived from the bacterium Clostridium botulinum. Nine serotypes are known; seroptypes A and B have been formulated for clinical use. BoNTs cleave one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins: vesicle-associated membrane protein (VAMP), synaptosomal-associated protein 25 (SNAP-25), or syntaxin. Upon entry into the synaptic terminal, BoNT inhibits the exocytosis of neurotransmitter containing synaptic vesicles. Cliical effects begin developing within a week after injection into skeletal muscle, then wear off after 2–4 months, requiring repeat injection. Neutralizing antibodies may develop, reducing clinical effects. Newer toxin preparations under development are listed in a table.

Keywords

Botuinum neurotoxinserotypeBoNTClostridium botulinumSNARE proteinVAMP proteinStyntaxinneutralizing antibodiesletibotulinumtoxinABotulaxbotulinumtoxinEInnotox
Type
Chapter
Information
Manual of Botulinum Toxin Therapy , pp. 13 - 17
Publisher: Cambridge University Press
Print publication year: 2023

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References

Brin, MF, Boodhoo, TI, Pogoda, JM et al. (2009). Safety and tolerability of onabotulinumtoxinA in the treatment of facial lines: a meta-analysis of individual patient data from global clinical registration studies in 1678 participants. J Am Acad Dermatol, 61(6), 911–61. https://doi.org/10.1016/j.jaad.2009.06.040CrossRefGoogle Scholar
Brin, MF, Comella, CL, Jankovic, J, Lai, F, Naumann, M (2008). Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay. Move Disord, 23(10), 1353–60. https://doi.org/10.1002/mds.22157CrossRefGoogle ScholarPubMed
Chen, S (2012). Clinical uses of botulinum neurotoxins: current indications, limitations and future developments. Toxins, 4(10), 913–39. https://doi.org/10.3390/toxins4100913CrossRefGoogle ScholarPubMed
Chertow, DS, Tan, ET, Maslanka, SE et al (2006). Botulism in 4 adults following cosmetic injections with an unlicensed, highly concentrated botulinum preparation. JAMA, 296(20), 2476–9. https://doi.org/10.1001/jama.296.20.2476Google Scholar
Choudhury, S, Baker, MR, Chatterjee, S, Kumar, H (2021). Botulinum toxin: an update on pharmacology and newer products in development. Toxins, 13(1), 58. https://doi.org/10.3390/toxins13010058CrossRefGoogle ScholarPubMed
de Paiva, A, Meunier, FA, Molgó, J, Aoki, KR, Dolly, JO (1999). Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci U S A, 96(6), 3200–5. https://doi.org/10.1073/pnas.96.6.3200CrossRefGoogle ScholarPubMed
Donald, S, Elliott, M, Gray, B et al. (2018). A comparison of biological activity of commercially available purified native botulinum neurotoxin serotypes A1 to F1 in vitro, ex vivo, and in vivo. Pharmacol Res Perspect, 6(6), e00446. https://doi.org/10.1002/prp2.446CrossRefGoogle ScholarPubMed
Dong, M, Yeh, F, Tepp, WH et al. (2006). SV2 is the protein receptor for botulinum neurotoxin A. Science, 312(5773), 592–6. https://doi.org/10.1126/science.1123654CrossRefGoogle ScholarPubMed
Dressler, D, Benecke, R (2003). Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis. Eur Neurol, 49(1), 34–8. https://doi.org/10.1159/000067023Google Scholar
Durham, PL, Cady, R, Cady, R (2004). Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache, 44(1), 33–5. https://doi.org/10.1111/j.1526-4610.2004.04007.xGoogle Scholar
Foran, PG. Mohammed, N, Lisk, GO et al. (2003). Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A. Basis for distinct durations of inhibition of exocytosis in central neurons. J Biol Chem, 278(2), 1363–71. https://doi.org/10.1074/jbc.M209821200CrossRefGoogle Scholar
Gelb, DJ, Yoshimura, DM, Olney, RK, Lowenstein, DH, Aminoff, MJ (1991). Change in pattern of muscle activity following botulinum toxin injections for torticollis. Ann Neurol, 29(4), 370–6. https://doi.org/10.1002/ana.410290407CrossRefGoogle ScholarPubMed
Kutschenko, A, Reinert, M-C, Krez, N, Liebetanz, D, Rummel, A (2017). BoNT/AB hybrid maintains similar duration of paresis as BoNT/A wild-type in murine running wheel assay. Neurotoxicology, 59, 1–8. https://doi.org/10.1016/j.neuro.2016.12.008CrossRefGoogle ScholarPubMed
Lungu, C, Karp, BI, Alter, K, Zolbrod, R, Hallett, M (2011). Long-term follow-up of botulinum toxin therapy for focal hand dystonia: outcome at 10 years or more. Mov Disord, 26(4), 750–3. https://doi.org/10.1002/mds.23504Google Scholar
Montal, M (2009). Translocation of botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel. Toxicon, 54(5), 565–9. https://doi.org/10.1016/j.toxicon.2008.11.018Google Scholar
Moore, AP, Naumann, M (2003). Handbook of Botulinum Toxin Treatment, 2nd ed. Malden, MA: Blackwell Science.Google Scholar
Naumann, M, Jankovic, J (2004). Safety of botulinum toxin type A: a systematic review and meta-analysis. CurrMed Res Opin, 20(7), 981–90. https://doi.org/10.1185/030079904125003962Google Scholar
Purkiss, J, Welch, M, Doward, S, Foster, K (2000). Capsaicin-stimulated release of substance P from cultured dorsal root ganglion neurons: involvement of two distinct mechanisms. Biochem Pharmacol, 59(11), 1403–6. https://doi.org/10.1016/s0006–2952(00)00260-4CrossRefGoogle ScholarPubMed
Rasetti-Escargueil, C, Popoff, MR (2020). Engineering botulinum neurotoxins for enhanced therapeutic applications and vaccine development. Toxins, 13(1). https://doi.org/10.3390/toxins13010001Google Scholar
Simpson, LL (1981). The origin, structure, and pharmacological activity of botulinum toxin. Pharmacol Rev, 33(3), 155–88.Google ScholarPubMed
Tighe, AP, Schiavo, G (2013). Botulinum neurotoxins: mechanism of action. Toxicon, 67, 87–93. https://doi.org/10.1016/j.toxicon.2012.11.011CrossRefGoogle ScholarPubMed
Zhang, S. Masuyer, G, Zhang, J et al. (2017). Identification and characterization of a novel botulinum neurotoxin. Nat Commun, 8, 14130. https://doi.org/10.1038/ncomms14130CrossRefGoogle ScholarPubMed

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