Comparison between botulinum neurotoxin type A2 and type A1 by electrophysiological study in healthy individuals

Mukai, Yohei; Shimatani, Yoshimitsu; Sako, Wataru; Asanuma, Kotaro; Nodera, Hiroyuki; Sakamoto, Takashi; Izumi, Yuishin; Kohda, Tomoko; Kozaki, Shunji; Kaji, Ryuji

doi:10.1016/j.toxicon.2013.12.012

Cited by 21 publications

(23 citation statements)

References 22 publications

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“…Nevertheless, this assay is useful in assessing duration of action of BoNTs after injection of sub-lethal amounts, whereas the DAS assay appeared more useful for determining onset of action. Comparative analysis of the onset of local paralysis as measured by the DAS assay indicated an earlier onset of action by BoNT/A2 (Figure 3), which is in agreement with previous data suggesting greater in vivo potency after local injection (21, 24), as well as faster neuronal cell entry and greater potency in cultured neurons (15, 16). The duration of action as measured by Rotarod was similar for BoNT/A1 and A2, which also is in agreement with previous observations in vivo (24) and in cultured neurons (17).…”

Section: Discussionsupporting

confidence: 91%

“…Comparative analysis of the onset of local paralysis as measured by the DAS assay indicated an earlier onset of action by BoNT/A2 (Figure 3), which is in agreement with previous data suggesting greater in vivo potency after local injection (21, 24), as well as faster neuronal cell entry and greater potency in cultured neurons (15, 16). The duration of action as measured by Rotarod was similar for BoNT/A1 and A2, which also is in agreement with previous observations in vivo (24) and in cultured neurons (17). Onset of local paralysis by BoNT/A3 was slightly delayed, and duration of action was significantly shorter, confirming previous observations of lowered potency and shorter duration of activity in cultured neurons (16, 17).…”

Section: Discussionsupporting

confidence: 91%

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In vivo onset and duration of action varies for botulinum neurotoxin A subtypes 1-5

Pellett

Tepp

Whitemarsh

et al. 2015

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To date, over 40 subtypes of botulinum neurotoxins (BoNTs) have been identified. BoNTs are classified into 7 serotypes distinguished primarily by their antigenic properties, but also characterized by their unique SNARE targets and cleavage sites, host specificity, and duration of action. Sequencing efforts in the last decade have identified several subtypes within the serotypes. Subtypes are currently defined as distinct based solely on amino acid sequence comparison, with a similarity cut-off of 2.5 % difference. Ten subtypes have been identified for BoNT/A, which is the serotype associated with the most severe human botulism and also the most commonly used serotype for clinical purposes. Analyses of several of these subtypes have revealed distinct characteristics, ranging from differences in cell entry and enzyme kinetics to differences in potency in mice and cell-model specific potency. A long-term activity study in cultured primary neurons has indicated that BoNT/A1, 2, 4, and 5 have a similar duration of action, whereas BoNT/A3 has a significantly shorter duration of action. This report describes an in vivo mouse study, showing that after local injection BoNT/A2 resulted in faster onset of local paralysis than BoNT/A1, 3, 4, and 5, whereas BoNT/A3 resulted in significantly faster recovery of motor-neuron deficiency.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

In vivo onset and duration of action varies for botulinum neurotoxin A subtypes 1-5

Pellett

Tepp

Whitemarsh

et al. 2015

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“…A comparable onset and duration of action among them was found without significant adverse effects (Mukai et al, 2014). Currently, a Phase 2 clinical trial performed in Japan is evaluating efficacy and safety of the use of BoNT/A2 for the treatment of poststroke lower limb spasticity (https://clinicaltrials.gov/show/NCT01910363) (Kaji et al, 2015).…”

Section: Pharmacologymentioning

confidence: 66%

Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology

et al. 2017

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The study of botulinum neurotoxins (BoNT) is rapidly progressing in many aspects. Novel BoNTs are being discovered owing to next generation sequencing, but their biologic and pharmacological properties remain largely unknown. The molecular structure of the large protein complexes that the toxin forms with accessory proteins, which are included in some BoNT type A1 and B1 pharmacological preparations, have been determined. By far the largest effort has been dedicated to the testing and validation of BoNTs as therapeutic agents in an ever increasing number of applications, including pain therapy. BoNT type A1 has been also exploited in a variety of cosmetic treatments, alone or in combination with other agents, and this specific market has reached the size of the one dedicated to the treatment of medical syndromes. The pharmacological properties and mode of action of BoNTs have shed light on general principles of neuronal transport and protein-protein interactions and are stimulating basic science studies. Moreover, the wide array of BoNTs discovered and to be discovered and the production of recombinant BoNTs endowed with specific properties suggest novel uses in therapeutics with increasing disease/symptom specifity. These recent developments are reviewed here to provide an updated picture of the biologic mechanism of action of BoNTs, of their increasing use in pharmacology and in cosmetics, and of their toxicology.

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“…Mukai and colleagues 16 were the first to report a comparative study of A2NTX and A1LL in healthy humans. In this study, 10units of A1LL and 6.5units of A2NTX were injected into EDB muscle on each side in the same subject.…”

Section: Clinical Researchmentioning

confidence: 99%