Different time courses of recovery after poisoning with botulinum neurotoxin serotypes A and E in humans

doi:10.1016/S0304-3940(98)00775-7

Neuroscience Letters

Volume 256, Issue 3, 13 November 1998, Pages 135-138

https://doi.org/10.1016/S0304-3940(98)00775-7 Get rights and content

Abstract

Botulinum toxin serotypes A and E (BoNT/A and /E) cleave the carboxy-terminus of synaptosomal associated protein-25 (SNAP-25) removing nine and 26 residues, respectively. To investigate the effect of these lesions of the same target molecule, 11 volunteers were injected with 3 IU of BoNT/A in the extensor digitorum brevis (EDB) muscle of one foot and with 3 IU of BoNT/E in the contralateral one. In addition, seven volunteers were similarly injected with mixtures of BoNT/A+BoNT/E. Compound muscular action potential (CMAP) was measured at different time intervals and the percentage variation of CMAP (%CMAP) was calculated. Unexpectedly, a much faster recovery of %CMAP after BoNT/E injections was observed. Double poisoned EBD muscles recovered similarly to BoNT/E. So, a larger deletion of the SNAP-25 molecule caused by BoNT/E leads to a faster functional recovery.

Section snippets

Acknowledgements

This work was supported by Telethon-Italia grant no. 1068.

References (17)

R Eleopra et al.
botulinum neurotoxin serotype C: a novel effective botulinum toxin therapy in human
Neurosci. Lett.
(1997)
G Borodic et al.
botulinum toxin therapy, immunologic resistance
Neurology
(1996)
M Brin
botulinum toxin: chemistry, pharmacology, toxicity, and immunology
Muscle Nerve
(1997)
M Cherington
Clinical spectrum of Botulism
Muscle Nerve
(1998)
R Eleopra et al.
botulinum toxin serotype C treatment in subjects affected by focal dystonia and resistant to botulinum toxin serotype A
Neurology
(1998)
P.E Greene et al.
Response to botulinum toxin F in seronegative botulinum toxin A-resistant patients
Mov. Disord.
(1996)
J.A Hamjian et al.
Serial neurophysiological studies of intramuscular botulinum A toxin in man
Muscle Nerve
(1994)
Jankovic, J. and Hallett, M. (Eds.), Therapy With Botulinum Toxin, Marcel Dekker, New York,...

There are more references available in the full text version of this article.

Cited by (179)

A look at the future—new BoNTs and delivery systems in development: What it could mean in the clinic
2023, Toxicon
Despite the expanding clinical utility of botulinum neurotoxins, there remain problems to be solved for attaining the best outcome. The efficacy and safety need to be reconsidered for commercially available preparations all derived from subtype A1 or B1. Emerging new toxins include A2 or A6 subtypes or engineered toxins with less spread, more potency, longer durations of action, less antigenicity and better safety profile than currently used preparations. Non-toxic BoNTs with a few amino acid replacements of the light chain (LC) may have a role as a drug-delivery system if the toxicity is abolished entirely. At present, efficacy of these BoNTs in animal botulism was demonstrated.
How does botulinum toxin really work?
2023, International Review of Neurobiology
Over the past 30 years, Botulinum toxin (BoNT) has emerged as an effective and safe therapeutic tool for a number of neurological conditions, including dystonia. To date, the exact mechanism of action of BoNT in dystonia is not fully understood. Although it is well known that BoNT mainly acts on the neuromuscular junction, a growing body of evidence suggests that the therapeutic effect of BoNT in dystonia may also depend on its ability to modulate peripheral sensory feedback from muscle spindles. Animal models also suggest a retrograde and anterograde BoNT transportation from the site of injection to central nervous system structures. In humans, however, BoNT central effects seem to depend on the modulation of afferent input rather than on BoNT transportation. In this chapter, we aimed to report and discuss research evidence providing information on the possible mechanisms of action of BoNT in relation to treatment of dystonia.
Simultaneous determination of BoNT/A and /E using an electrochemical sandwich immunoassay based on the nanomagnetic immunosensing platform
2022, Chemosphere
Citation Excerpt :
Thereby, a sustained neurotransmitter release blockade of the amino acid residues may occur by the BoNTs. In this respect, acetylcholine release inhibition is expected to be caused by the BoNT/E in the wake of the recovery of function, having a similar time course compared to that caused by BoNT/A (Eleopra et al., 1998). The popular method for detection of BoNTs is mouse assay, giving rise to a typical toxin at the low concentration of 10 pg mL−1 (Sharma and Whiting, 2005).
Developing new ultrasensitive assays for the detection of the presence, and determination of the serotype of the most poisonous material known i.e. botulinum neurotoxin (BoNT) is vital to human health and the wellbeing of the surrounding environment. Here, an electrochemical sandwich immunoassay with high sensitivity is adopted to achieve simultaneous determination of BoNT serotypes A and E based on polystyrene@polydopamine/Cd²⁺ and Ag nanoparticles acting as monoclonal antibody labels. Two well-separated peaks with strong electrochemical signals are generated by the labels, allowing for the simultaneous detection of two analytes existing on the electrode. To obtain well-oriented polyclonal antibodies immobilization, boronic acid is directly attached to the magnetic core/metal-organic framework (MOF) shell nanoagent surfaces without the requirement of a long and flexible spacer. Accordingly, it is possible to directly detect the metal ion labels through square wave voltammetry without the metal pre-concentration step. This results in distinct and well-defined voltammetric peaks, pertaining to each sandwich-type immunocomplexes. The limits of detection of BoNT/A and BoNT/E analyses were found to be 0.04 and 0.16 pg mL⁻¹ with the linear dynamic ranges of 0.1–1000 and 0.5–1000 pg mL⁻¹, respectively. Based on the obtained results, this immunosensor has the wide linear ranges, while also exhibiting low limits of detection along with good stability and reproducibility.
Clinical duration of action of different botulinum toxin types in humans
2020, Toxicon
The Botulinum NeuroToxin (BoNT) comprises several serotypes with distinct properties, mechanisms of action, sensitivity and duration of effect in different species. The serotype A (BoNT/A) is the prevalent neurotoxin applied in human's disease. In this paper we present an overview of the current knowledge regarding the duration of effect and the neuromuscular sprouting of different BoNT serotypes in humans. Then, we report the original results of a study in healthy subjects treated with BoNT/A, B, C and F using different neurophysiological techniques. Twelve healthy volunteers (7 men, 5 women) are treated with BoNT/A, B, C and F or placebo in Abductor digiti minimi (ADM) muscle of the hand. Before and after injections, an extensive neurophysiological study is performed with the CMAP amplitude variation, Multi-Motor Unit Action Potentials (MUAPs) analysis, the Turns/Amplitude ratio of interference pattern (IP) and determination of jitter and Fiber Density (FD) at single-fiber electromyography (SFEMG), at week 2 (w2), 4 (w4), 6 (w6) and 8 (w8). A maximal neuromuscular block is obtained at w2 for all the serotypes. Afterwards, the CMAP trend appear similar for BoNT/A, B, and C while, BoNT/F shows a faster recover. Multi-MUAPs analysis and IP detect mild changes at w2 for all serotypes, except for BoNT/F that shows a greater change since w4. SFEMG have minimal changes in FD while, Jitter increase at w2 with a slower decrease over the time for all BoNTs. In conclusion, BoNT/F has earlier sprouting and complete recovery at w8. Other serotypes present a slower and similar profile. The EMG appear useful to study the functional recovery in humans, and these results should provide new evidence for assessing different serotypes. These findings improve our knowledge regarding the methods to evaluate duration of effects and dose equivalents in different serotypes, that in the future could change the clinicians strategy for disease-tailored BoNT therapies.
Botulinum toxin: Pharmacology and injectable administration for the treatment of primary hyperhidrosis
2020, Journal of the American Academy of Dermatology
Hyperhidrosis is a dermatological condition defined by excessive sweating beyond thermoregulatory needs with significant effects on patients' quality of life. Hyperhidrosis is categorized as primary or secondary: primary hyperhidrosis is mostly focal and idiopathic, whereas secondary hyperhidrosis is commonly generalized and caused by an underlying medical condition or use of medications. Various surgical and nonsurgical therapies exist for primary hyperhidrosis. Although botulinum toxin is one of the deadliest toxins known, when used in small doses, it is one of the most effective therapies for primary hyperhidrosis. Botulinum toxin injections are widely used as a second-line primary hyperhidrosis treatment option once topical treatment strategies have failed. This article provides an overview of the commercially available botulinum toxin formulations and their applications in the treatment of primary hyperhidrosis.
Safety and pharmacodynamics of a novel recombinant botulinum toxin E (rBoNT-E): Results of a phase 1 study in healthy male subjects compared with abobotulinumtoxinA (Dysport®)
2019, Journal of the Neurological Sciences
Naturally occurring botulinum toxin (BoNT) serotypes have different pharmacological features of therapeutic and aesthetic interest. This phase 1, double-blind, placebo-controlled study (EudraCT: 2016–002609-20) assessed safety, tolerability and pharmacodynamics (PD) of the first recombinant BoNT serotype E (rBoNT-E) versus abobotulinumtoxinA (Dysport®), administered to extensor digitorum brevis (EDB) of healthy males. Subjects were randomised 3:1 (n = 28) to single ascending rBoNT-E (0.04–3.6 ng) doses or placebo. A further 24 subjects received abobotulinumtoxinA (20, 40, or 70 U) or placebo. PD were assessed using compound muscle action potential (CMAP) amplitude. Demographics were similar between groups. All rBoNT-E doses were well tolerated (no severe treatment-emergent adverse events [TEAEs], serious adverse events, or treatment-related toxicities). Most TEAEs were mild/moderate and treatment-unrelated. rBoNT-E had a faster onset of action (days 1–2 post-injection), greater peak effect (>90% CMAP inhibition), and shorter duration of effect at highest tested doses versus abobotulinumtoxinA (onset of action ≤7 days post-injection; 70% maximal CMAP inhibition). rBoNT-E duration of effect was 2–7 weeks versus >26 weeks for abobotulinumtoxinA. Dose-dependent effects were observed for magnitude and duration of EDB CMAP inhibition, plateauing at 0.9 and 3.6 ng. rBoNT-E demonstrated a good safety profile and a PD profile that may address unmet therapeutic and aesthetic patient needs.

View all citing articles on Scopus

View full text

Different time courses of recovery after poisoning with botulinum neurotoxin serotypes A and E in humans

Abstract

Section snippets

Acknowledgements

Neurosci. Lett.

botulinum toxin therapy, immunologic resistance

Neurology

botulinum toxin: chemistry, pharmacology, toxicity, and immunology

Muscle Nerve

Clinical spectrum of Botulism

Muscle Nerve

botulinum toxin serotype C treatment in subjects affected by focal dystonia and resistant to botulinum toxin serotype A

Neurology

Response to botulinum toxin F in seronegative botulinum toxin A-resistant patients

Mov. Disord.

Serial neurophysiological studies of intramuscular botulinum A toxin in man

Muscle Nerve