Pharmaceutical Nanotechnology

Author(s): S. Danish Kadir*

DOI: 10.2174/2211738511666230825150259

Industrial Production and Therapeutic Application of Botulinum Neurotoxin: The Role of C. botulinum Type A

Page: [99 - 107] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Botulinum neurotoxin has remarkably transitioned from a food safety hazard and biological warfare to an effective therapeutic drug. Currently, botulinum neurotoxins have seven serotypes (BoNT/A-G) in the form of protein complexes produced by Clostridium, a gram-positive and sporeforming bacteria. The conversion of toxins into useful drug substances of choice using the biotechnological process is tremendously increasing. Recent studies have shown that Botulinum neurotoxin-A (BoNT/A) has different biological activities and potencies in experimental and clinical conditions. They also indicate that the manufacturing process influences the potency and efficacy of BoNT/A drugs. Thus, this review focuses on the following criteria: detailed Fed-batch operation that includes the upstream and downstream processing of BoNT/A, the underlying mechanism behind the neurotoxic effect, and commercially available FDA-approved BoNT/A products and their therapeutic uses. Still, some research gaps exist in the mechanism for the treatment of psychiatric disorders.

Graphical Abstract

[1]
Dressler D. Botulinum toxin drugs: Brief history and outlook. J Neural Transm 2016; 123(3): 277-9.
[http://dx.doi.org/10.1007/s00702-015-1478-1] [PMID: 26559824]
[2]
U.S. Department of Health & Human Services. 2021.About botulism. Available from: https://www.cdc.gov/botulism/general.html
[3]
Nigam PK, Nigam A. Botulinum toxin. Indian J Dermatol 2010; 55(1): 8-14.
[http://dx.doi.org/10.4103/0019-5154.60343] [PMID: 20418969]
[4]
Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. J Pediatr Ophthalmol Strabismus 1980; 17(1): 21-5.
[http://dx.doi.org/10.3928/0191-3913-19800101-06] [PMID: 7365644]
[5]
Keith AF. Molecular aspects of botulinum neurotoxin. Springer 2014; p. 4.
[http://dx.doi.org/10.1007/978-1-4614-9453-9]
[6]
National Institutes of Health. NCI Drug Dictionary. 2022. Available from: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/botulinum-toxin-type-a
[7]
Samul D. Beneficial and harmful roles of bacteria from the clostridium genus. Acta Biochim Pol 2013; 60(4): 515-21.
[http://dx.doi.org/10.18388/abp.2013_2015]
[8]
Sonone TP. Botox and dermal fillers in orthodontics: A review. J Pharm Bioallied Sci 2022; 14 (Suppl. 1): S60-4.
[http://dx.doi.org/10.4103/jpbs.jpbs_184_22]
[9]
Raatjes GJ, Smelt JP. Clostridium botulinum can grow and form toxin at pH values lower than 4.6. Nature 1979; 281(5730): 398-9.
[http://dx.doi.org/10.1038/281398a0]
[10]
Whitcup S, Hillcup M, Eds. Botulinum Toxin Therapy Handbook of Experimental Pharmacology. Cham: Springer 2022; Vol. 3.
[11]
Prager G. No Title. (1st ed.), John Willey and Sons Inc 2018.
[12]
Frevert J. Content of botulinum neurotoxin in botox®vistabel®, dysport®azzalure®, and xeomin®bocouture. Drugs R D 2010; 10(2): 67-73.
[http://dx.doi.org/10.2165/11584780-000000000-00000] [PMID: 20698714]
[13]
Shukla HD, Sharma SK. Clostridium botulinum: A bug with beauty and weapon. Crit Rev Microbiol 2004; 31(1): 11-8.
[http://dx.doi.org/10.1080/10408410590912952]
[14]
Keith A. Foster (2014) Molecular aspects of Botulinum Neurotoxin. Springer 2014; Vol.4.
[http://dx.doi.org/10.1007/978-1-4614-9453-9]
[15]
Fu Z, Chen S, Baldwin MR, et al. Light chain of botulinum neurotoxin serotype A: Structural resolution of a catalytic intermediate. Biochemistry 2006; 45(29): 8903-11.
[http://dx.doi.org/10.1021/bi060786z] [PMID: 16846233]
[16]
Tighe AP, Schiavo G. Botulinum neurotoxins: Mechanism of action. Toxicon 2013; 67: 87-93.
[http://dx.doi.org/10.1016/j.toxicon.2012.11.011] [PMID: 23201505]
[17]
Lorenc ZP, Kenkel JM, Fagien S, et al. IncobotulinumtoxinA (Xeomin): Background, mechanism of action, and manufacturing. Aesthet Surg J 2013; 33(1): 18S-22S.
[PMID: 23515195]
[18]
Barnes M. Botulinum toxin - mechanisms of action and clinical use in spasticity. J Rehabil Med 2003; 35(41 Suppl): 56-9.
[http://dx.doi.org/10.1080/16501960310010151] [PMID: 12817658]
[19]
Rowland LP. Stroke, spasticity, and botulinum toxin. N Engl J Med 2002; 347(6): 382-3.
[http://dx.doi.org/10.1056/NEJMp020071] [PMID: 12167679]
[20]
Davletov B, Bajohrs M, Binz T. Beyond BOTOX: Advantages and limitations of individual botulinum neurotoxins. Trends Neurosci 2005; 28(8): 446-52.
[http://dx.doi.org/10.1016/j.tins.2005.06.001] [PMID: 15979165]
[21]
Rosales RL, Chua-Yap AS. Evidence-based systematic review on the efficacy and safety of botulinum toxin-A therapy in post-stroke spasticity. J Neural Transm 2008; 115(4): 617-23.
[http://dx.doi.org/10.1007/s00702-007-0869-3] [PMID: 18322637]
[22]
Maroto Rodríguez B, Stoica BTL, Toledano Fernández N, Genol Saavedra I. Treatment for functional epiphora with botulinum toxin-A versus lateral tarsal strip in a randomized trial. Archivos de la Sociedad Española de Oftalmología (English Edition) 2022; 97(10): 549-57.
[http://dx.doi.org/10.1016/j.oftale.2022.06.011] [PMID: 35879178]
[23]
Spiegel LL, Ostrem JL, Bledsoe IO. FDA approvals and consensus guidelines for botulinum toxins in the treatment of dystonia. Toxins 2020; 12(5): 332.
[http://dx.doi.org/10.3390/toxins12050332] [PMID: 32429600]
[24]
Alster TS, Harrison IS. Alternative clinical indications of botulinum toxin. Am J Clin Dermatol 2020; 21(6): 855-0.
[http://dx.doi.org/10.1007/s40257-020-00532-0] [PMID: 32651806]
[25]
Hess K, Schmitt M, Wabbels B. Periorbital injections of botulinum toxin a: A novel therapeutic option for convergence spasm in neuro-psychiatric disorders. J Neurol 2022; 269(1): 243-50.
[http://dx.doi.org/10.1007/s00415-021-10613-7] [PMID: 34047854]
[26]
Argyriou AA, Dermitzakis EV, Vlachos GS, Vikelis M. Long‐term adherence, safety, and efficacy of repeated onabotulinumtoxinA over five years in chronic migraine prophylaxis. Acta Neurol Scand 2022; 145(6): 676-83.
[http://dx.doi.org/10.1111/ane.13600] [PMID: 35170031]
[27]
Clarkson BD, Karim HT, Chermansky CJ, et al. Changes in brain response to urgency before and after treatment of urgency urinary incon-tinence with onabotulinumtoxin A. Neurourol Urodyn 2022; 41(8): 1703-10.
[http://dx.doi.org/10.1002/nau.25012] [PMID: 35904238]
[28]
Moftah NH, Moftah NH. Non-pharmacologic treatment for acne vulgaris. CosmoDerma 2022; 2: 51.
[http://dx.doi.org/10.25259/CSDM_49_2022]
[29]
Rasteau S, Savoldelli C, Winter C, Lerhe B, Castillo L, Kestemont P. Botulinum toxin type A for the treatment of excessive gingival display – A systematic review. J Stomatol Oral Maxillofac Surg 2022; 123(6): e717-23.
[http://dx.doi.org/10.1016/j.jormas.2022.05.016]
[30]
Zanchi M, Favot F, Bizzarini M, Piai M, Donini M, Sedona P. Botulinum toxin type-A for the treatment of inverse psoriasis. J Eur Acad Dermatol Venereol 2008; 22(4): 431-6.
[http://dx.doi.org/10.1111/j.1468-3083.2007.02457.x] [PMID: 18363911]
[31]
Giannantoni A, Mearini E, Del Zingaro M, Porena M. Six-year follow-up of botulinum toxin A intradetrusorial injections in patients with refractory neurogenic detrusor overactivity: Clinical and urodynamic results. Eur Urol 2009; 55(3): 705-12.
[http://dx.doi.org/10.1016/j.eururo.2008.08.048] [PMID: 18814955]
[32]
Lowe NJ, Glaser DA, Eadie N, Daggett S, Kowalski JW, Lai PY. Botulinum toxin type A in the treatment of primary axillary hyperhidrosis: A 52-week multicenter double-blind, randomized, placebo-controlled study of efficacy and safety. J Am Acad Dermatol 2007; 56(4): 604-11.
[http://dx.doi.org/10.1016/j.jaad.2007.01.009] [PMID: 17306417]
[33]
Dressler D, Pan L, Su J, Teng F, Jin L. Lantox—The chinese botulinum toxin drug—complete english bibliography and] comprehensive formalised literature review. Toxins 2021; 13(6): 370.
[http://dx.doi.org/10.3390/toxins13060370] [PMID: 34067301]
[34]
Pellett S, Yaksh T, Ramachandran R. Current status and future directions of botulinum neurotoxins for targeting pain processing. Toxins 2015; 7(11): 4519-63.
[http://dx.doi.org/10.3390/toxins7114519] [PMID: 26556371]