Toxins

Research

Jump to: Review

12 pages, 2182 KiB

Open AccessCommunication

The Extreme Ends of the Treatment Response Spectrum to Botulinum Toxin in Cervical Dystonia

by Sara Samadzadeh, Raphaela Brauns and Harald Hefter

Toxins 2021, 13(1), 22; https://doi.org/10.3390/toxins13010022 - 31 Dec 2020

Cited by 6 | Viewed by 2456

Abstract

Background: The response to BoNT is not uniform; a broad spectrum of responses and side-effects usually occurs. This study aimed to show special cervical dystonia cases with therapy response very different to normal treatment course which indicate the extreme ends of therapy spectrum. [...] Read more.

Background: The response to BoNT is not uniform; a broad spectrum of responses and side-effects usually occurs. This study aimed to show special cervical dystonia cases with therapy response very different to normal treatment course which indicate the extreme ends of therapy spectrum. Patients: Clinical data and course of treatment of five long-term treated patients with cervical dystonia out of therapy response norms are presented: a patient who was supersensitive to standard dose and has required dose adjustment to lower dose of BoNT; one patient who worsened under a standard dose, but responded excellently to twice the standard dose; one insensitive patient who responded poorly for years to a dose well above the standard dose, but responded when dose was further increased; and two patients with a totally different response pattern to BoNT/A preparation 1, but the development of a neutralizing antibody induced secondary treatment failure in both cases and a totally different response after switch to BoNT/A preparation 2. Conclusions: These five patients indicate that the response of a patient to a BoNT preparation may be unexpected. Therefore, cautious onset of BoNT therapy is recommended as well as consequent dose adjustment later on and even switch to another BoNT/A preparation when a patient has already developed NABs against BoNT/A. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

► Show Figures

Figure 1

14 pages, 703 KiB

Open AccessArticle

Detection of Active BoNT/C and D by EndoPep-MS Using MALDI Biotyper Instrument and Comparison with the Mouse Test Bioassay

by Ilenia Drigo, Elena Tonon, Simone Pascoletti, Fabrizio Anniballi, Suzanne R. Kalb and Luca Bano

Toxins 2021, 13(1), 10; https://doi.org/10.3390/toxins13010010 - 24 Dec 2020

Cited by 6 | Viewed by 2892

Abstract

Botulinum neurotoxins (BoNTs) are among the most poisonous known biological substances, and therefore the availability of reliable, easy-to use tools for BoNT detection are important goals for food safety and human and animal health. The reference method for toxin detection and identification is [...] Read more.

Botulinum neurotoxins (BoNTs) are among the most poisonous known biological substances, and therefore the availability of reliable, easy-to use tools for BoNT detection are important goals for food safety and human and animal health. The reference method for toxin detection and identification is the mouse bioassay (MBA). An EndoPep-MS method for BoNT differentiation has been developed based on mass spectrometry. We have validated and implemented the EndoPep-MS method on a Bruker MALDI Biotyper for the detection of BoNT/C and D serotypes. The method was extensively validated using experimentally and naturally contaminated samples comparing the results with those obtained with the MBA. Overall, the limit of detection (LoD) for both C and D toxins were less than or equal to two mouse lethal dose 50 (mLD₅₀) per 500 µL for all tested matrices with the exception of feces spiked with BoNT/C which showed signals not-related to specific peptide fragments. Diagnostic sensitivity, specificity and positive predictive value were 100% (95% CI: 87.66–100%), 96.08% (95% CI: 86.54–99.52%), and 93.33% (95% CI: 78.25–98.20%), respectively, and accuracy was 97.47% (95% CI: 91.15–99.69%). In conclusion, the tests carried out showed that the EndoPep-MS method, initially developed using more powerful mass spectrometers, can be applied to the Bruker MALDI Biotyper instrument with excellent results including for detection of the proteolytic activity of BoNT/C, BoNT/D, BoNT/CD, and BoNT/DC toxins. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

► Show Figures

Figure 1

11 pages, 1495 KiB

Open AccessArticle

Neurotrophic Properties of C-Terminal Domain of the Heavy Chain of Tetanus Toxin on Motor Neuron Disease

by Mireia Herrando-Grabulosa, Caty Casas, Kevin Talbot and José Aguilera

Toxins 2020, 12(10), 666; https://doi.org/10.3390/toxins12100666 - 21 Oct 2020

Cited by 2 | Viewed by 2438

Abstract

The carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts a neuroprotective effect in neurodegenerative diseases via the activation of signaling pathways related to neurotrophins, and also through inhibiting apoptotic cell death. Here, we demonstrate that Hc-TeTx preserves motoneurons from chronic [...] Read more.

The carboxyl-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) exerts a neuroprotective effect in neurodegenerative diseases via the activation of signaling pathways related to neurotrophins, and also through inhibiting apoptotic cell death. Here, we demonstrate that Hc-TeTx preserves motoneurons from chronic excitotoxicity in an in vitro model of amyotrophic lateral sclerosis. Furthermore, we found that PI3-K/Akt pathway, but not p21ras/MAPK pathway, is involved in their beneficial effects under chronic excitotoxicity. Moreover, we corroborate the capacity of the Hc-TeTx to be transported retrogradely into the spinal motor neurons and also its capacity to bind to the motoneuron-like cell line NSC-34. These findings suggest a possible therapeutic tool to improve motoneuron preservation in neurodegenerative diseases such as amyotrophic lateral sclerosis. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

► Show Figures

Graphical abstract

12 pages, 1736 KiB

Open AccessArticle

Development of An Innovative and Quick Method for the Isolation of Clostridium botulinum Strains Involved in Avian Botulism Outbreaks

by Thibault Le Gratiet, Typhaine Poezevara, Sandra Rouxel, Emmanuelle Houard, Christelle Mazuet, Marianne Chemaly and Caroline Le Maréchal

Toxins 2020, 12(1), 42; https://doi.org/10.3390/toxins12010042 - 10 Jan 2020

Cited by 8 | Viewed by 5189

Abstract

Avian botulism is a serious neuroparalytic disease mainly caused by a type C/D botulinum neurotoxin produced by Clostridium botulinum group III, one of the entwined bacterial species from the Clostridium novyi sensu lato genospecies. Its isolation is very challenging due to the absence [...] Read more.

Avian botulism is a serious neuroparalytic disease mainly caused by a type C/D botulinum neurotoxin produced by Clostridium botulinum group III, one of the entwined bacterial species from the Clostridium novyi sensu lato genospecies. Its isolation is very challenging due to the absence of selective media and the instability of the phage carrying the gene encoding for the neurotoxin. The present study describes the development of an original method for isolating C. botulinum group III strains. Briefly, this method consists of streaking the InstaGene matrix extraction pellet on Egg Yolk Agar plates and then collecting the colonies with lipase and lecithinase activities. Using this approach, it was possible to isolate 21 C. novyi sensu lato strains from 22 enrichment broths of avian livers, including 14 toxic strains. This method was successfully used to re-isolate type C, D, C/D, and D/C strains from liver samples spiked with five spores per gram. This method is cheap, user-friendly, and reliable. It can be used to quickly isolate toxic strains involved in avian botulism with a 64% success rate and C. novyi sensu lato with a 95% rate. This opens up new perspectives for C. botulinum genomic research, which will shed light on the epidemiology of avian botulism. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

► Show Figures

Figure 1

17 pages, 1688 KiB

Open AccessArticle

Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes

by Jean Louis Bossu, Laetitia Wioland, Frédéric Doussau, Philippe Isope, Michel R. Popoff and Bernard Poulain

Toxins 2020, 12(1), 36; https://doi.org/10.3390/toxins12010036 - 06 Jan 2020

Cited by 5 | Viewed by 3343

Abstract

Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurological disorders in animals. ETX can bind to the white matter of the brain and the oligodendrocytes, which are the cells forming the myelin sheath around neuron axons in the [...] Read more.

Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurological disorders in animals. ETX can bind to the white matter of the brain and the oligodendrocytes, which are the cells forming the myelin sheath around neuron axons in the white matter of the central nervous system. After binding to oligodendrocytes, ETX causes demyelination in rat cerebellar slices. We further investigated the effects of ETX on cerebellar oligodendrocytes and found that ETX induced small transmembrane depolarization (by ~ +6.4 mV) in rat oligodendrocytes primary cultures. This was due to partial inhibition of the transmembrane inward rectifier potassium current (Kir). Of the two distinct types of Kir channel conductances (~25 pS and ~8.5 pS) recorded in rat oligodendrocytes, we found that ETX inhibited the large-conductance one. This inhibition did not require direct binding of ETX to a Kir channel. Most likely, the binding of ETX to its membrane receptor activates intracellular pathways that block the large conductance Kir channel activity in oligodendrocyte. Altogether, these findings and previous observations pinpoint oligodendrocytes as a major target for ETX. This supports the proposal that ETX might be a cause for Multiple Sclerosis, a disease characterized by myelin damage. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

► Show Figures

Figure 1

19 pages, 4999 KiB

Open AccessArticle

Looking for the X Factor in Bacterial Pathogenesis: Association of orfX-p47 Gene Clusters with Toxin Genes in Clostridial and Non-Clostridial Bacterial Species

by Maria B. Nowakowska, François P. Douillard and Miia Lindström

Toxins 2020, 12(1), 19; https://doi.org/10.3390/toxins12010019 - 31 Dec 2019

Cited by 5 | Viewed by 3970

Abstract

The botulinum neurotoxin (BoNT) has been extensively researched over the years in regard to its structure, mode of action, and applications. Nevertheless, the biological roles of four proteins encoded from a number of BoNT gene clusters, i.e., OrfX1-3 and P47, are unknown. Here, [...] Read more.

The botulinum neurotoxin (BoNT) has been extensively researched over the years in regard to its structure, mode of action, and applications. Nevertheless, the biological roles of four proteins encoded from a number of BoNT gene clusters, i.e., OrfX1-3 and P47, are unknown. Here, we investigated the diversity of orfX-p47 gene clusters using in silico analytical tools. We show that the orfX-p47 cluster was not only present in the genomes of BoNT-producing bacteria but also in a substantially wider range of bacterial species across the bacterial phylogenetic tree. Remarkably, the orfX-p47 cluster was consistently located in proximity to genes coding for various toxins, suggesting that OrfX1-3 and P47 may have a conserved function related to toxinogenesis and/or pathogenesis, regardless of the toxin produced by the bacterium. Our work also led to the identification of a putative novel BoNT-like toxin gene cluster in a Bacillus isolate. This gene cluster shares striking similarities to the BoNT cluster, encoding a bont/ntnh-like gene and orfX-p47, but also differs from it markedly, displaying additional genes putatively encoding the components of a polymorphic ABC toxin complex. These findings provide novel insights into the biological roles of OrfX1, OrfX2, OrfX3, and P47 in toxinogenesis and pathogenesis of BoNT-producing and non-producing bacteria. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

► Show Figures

Figure 1

11 pages, 1254 KiB

Open AccessArticle

Safety and Efficacy of Intracavernosal Injections of AbobotulinumtoxinA (Dysport^®) as Add on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 for Erectile Dysfunction—Case Studies

by Francois Giuliano, Charles Joussain and Pierre Denys

Toxins 2019, 11(5), 283; https://doi.org/10.3390/toxins11050283 - 21 May 2019

Cited by 14 | Viewed by 4384

Abstract

Erectile dysfunction (ED) is a highly prevalent condition with a variety of possible risk factors and/or etiologies. Despite significant advances regarding ED pharmacological management, there are still insufficient responders to existing pharmacological treatments e.g., approximately 30% of patients are insufficient responders to phosphodiesterase [...] Read more.

Erectile dysfunction (ED) is a highly prevalent condition with a variety of possible risk factors and/or etiologies. Despite significant advances regarding ED pharmacological management, there are still insufficient responders to existing pharmacological treatments e.g., approximately 30% of patients are insufficient responders to phosphodiesterase type 5 inhibitors (PDE5-Is). It has been recently proposed that botulinum toxin A intracavernosally (IC) delivered could be effective in these patients. Data from a retrospective uncontrolled single center study of 47 ED patients, consecutively recruited, insufficient responders to existing pharmacological treatments e.g., PDE5-Is or IC PGE1 injections treated with IC abobotulinumtoxinA 250 or 500 U as free combination with their existing treatment have been analyzed. Response rate, according to the International Index of Erectile Function-Erectile Function domain score, 6 weeks following IC abobotulinumtoxinA in combination with prior pharmacological treatment, was 54%. Two patients have reported mild penile pain on injection or during the 3 days following injection. Therapeutic efficacy did not seem to be influenced by the etiologies and/or risk factors for ED. Conversely, the less severe ED, the higher the response rate. Preliminary evidence for the therapeutical potential with acceptable safety of IC abobotulinumtoxinA as add-on therapy for ED not sufficiently responsive to standard therapy should be confirmed in randomized clinical trials. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

► Show Figures

Figure 1

Review

Jump to: Research

34 pages, 693 KiB

Open AccessReview

Therapeutic Use of Botulinum Neurotoxins in Dermatology: Systematic Review

by Emanuela Martina, Federico Diotallevi, Giulia Radi, Anna Campanati and Annamaria Offidani

Toxins 2021, 13(2), 120; https://doi.org/10.3390/toxins13020120 - 05 Feb 2021

Cited by 27 | Viewed by 5518

Abstract

Botulinum toxin is a superfamily of neurotoxins produced by the bacterium Clostridium Botulinum with well-established efficacy and safety profile in focal idiopathic hyperhidrosis. Recently, botulinum toxins have also been used in many other skin diseases, in off label regimen. The objective of this [...] Read more.

Botulinum toxin is a superfamily of neurotoxins produced by the bacterium Clostridium Botulinum with well-established efficacy and safety profile in focal idiopathic hyperhidrosis. Recently, botulinum toxins have also been used in many other skin diseases, in off label regimen. The objective of this manuscript is to review and analyze the main therapeutic applications of botulinum toxins in skin diseases. A systematic review of the published data was conducted, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Botulinum toxins present several label and off-label indications of interest for dermatologists. The best-reported evidence concerns focal idiopathic hyperhidrosis, Raynaud phenomenon, suppurative hidradenitis, Hailey–Hailey disease, epidermolysis bullosa simplex Weber–Cockayne type, Darier’s disease, pachyonychia congenita, aquagenic keratoderma, alopecia, psoriasis, notalgia paresthetica, facial erythema and flushing, and oily skin. Further clinical trials are still needed to better understand the real efficacy and safety of these applications and to standardize injection and doses protocols for off label applications. Full article

(This article belongs to the Special Issue Clostridium Neurotoxins)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Clostridium Neurotoxins

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI