Potency, Duration of Action, and Pharmacodynamics of Human Neurotoxins

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (15 December 2020) | Viewed by 21289

Special Issue Editors

Microbiology and Immunology, Medical College of Wisconsin, 8701 Watertown Plank Rd., Microbiology and Immunology, BSB-255, Milwaukee, WI 53226, USA
Interests: protein toxins; type-III effectors; structure-based mechanisms of toxin action; botulinum toxins; tetanus toxin; cellular microbiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural and synthetic neurotoxins utilize numerous mechanisms to intoxicate and persist in their hosts. For example, botulinum neurotoxins (BoNTs) are the most potent protein toxins for humans. BoNTs are produced by the anaerobic spore forming clostridia, primarily C. botulinum. Botulism is characterized by long-lasting flaccid paralysis due to the continuous block of neurotransmitter release at neuromuscular junctions. Genome sequencing has shown that BoNTs comprise a large and diverse protein family, with at least seven distinguishable serotypes and numerous subtypes within these serotypes. While the overall basis for entry into neurons and mechansim of cleavage and recogniton SNARE proteins are similar, individual BoNT serotypes and subtypes differ in potency, onset of symptoms, duration of action, pharmacodynamic behavior, and species specificity. Little is known about the mechanisms underlying the specificity of these biological characteristics. Research into these mechanisms will provide insights in the expansion of BoNT pharmaceutical potential and development of countermeasures and treatment modalities against botulism. This series welcomes primary articles and reviews that address the basis for the biological spectrum of the action of BoNTs and other neurotoxins on neurons, humans, and model systems, utilizing informatics, computational biology, and laboratory-based approaches.  

Dr. Sabine Pellett
Prof. Joseph Barbieri
Guest Editors

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Keywords

  • neurotoxins
  • botulinum neurotoxin
  • pharmacodynamics
  • pharmacokinetics
  • potency
  • duration

Published Papers (2 papers)

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Review

14 pages, 2295 KiB  
Review
Botulinum Toxin Type A to Improve Facial Symmetry in Facial Palsy: A Practical Guideline and Clinical Experience
by Carla de Sanctis Pecora and Danielle Shitara
Toxins 2021, 13(2), 159; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020159 - 18 Feb 2021
Cited by 18 | Viewed by 17654
Abstract
Unilateral peripheral facial nerve palsy jeopardizes quality of life, rendering psychological consequences such as low self-esteem, social isolation, anxiety, and depression. Among therapeutical approaches, use of Botulinum toxin type A (BoNT-A) on the nonparalyzed side has shown promising results and improvement of quality [...] Read more.
Unilateral peripheral facial nerve palsy jeopardizes quality of life, rendering psychological consequences such as low self-esteem, social isolation, anxiety, and depression. Among therapeutical approaches, use of Botulinum toxin type A (BoNT-A) on the nonparalyzed side has shown promising results and improvement of quality of life. Nevertheless, the correct technique is paramount, since over-injection of the muscles can result in lack of function, leading to a “paralyzed” appearance, and even worse, functional incompetence, which may cause greater distress to patients. Therefore, the objective of this article is to provide a practical guideline for botulinum toxin use in facial palsy. To this aim, adequate patient assessment, BoNT-A choice, injection plan and dosage, and injection techniques are covered. Full article
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25 pages, 465 KiB  
Review
Toxemia in Human Naturally Acquired Botulism
by Christine Rasetti-Escargueil, Emmanuel Lemichez and Michel R. Popoff
Toxins 2020, 12(11), 716; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12110716 - 13 Nov 2020
Cited by 17 | Viewed by 3038
Abstract
Human botulism is a severe disease characterized by flaccid paralysis and inhibition of certain gland secretions, notably salivary secretions, caused by inhibition of neurotransmitter release. Naturally acquired botulism occurs in three main forms: food-borne botulism by ingestion of preformed botulinum neurotoxin (BoNT) in [...] Read more.
Human botulism is a severe disease characterized by flaccid paralysis and inhibition of certain gland secretions, notably salivary secretions, caused by inhibition of neurotransmitter release. Naturally acquired botulism occurs in three main forms: food-borne botulism by ingestion of preformed botulinum neurotoxin (BoNT) in food, botulism by intestinal colonization (infant botulism and intestinal toxemia botulism in infants above one year and adults), and wound botulism. A rapid laboratory confirmation of botulism is required for the appropriate management of patients. Detection of BoNT in the patient’s sera is the most direct way to address the diagnosis of botulism. Based on previous published reports, botulinum toxemia was identified in about 70% of food-borne and wound botulism cases, and only in about 28% of infant botulism cases, in which the diagnosis is mainly confirmed from stool sample investigation. The presence of BoNT in serum depends on the BoNT amount ingested with contaminated food or produced locally in the intestine or wound, and the timeframe between serum sampling and disease onset. BoNT levels in patient’s sera are most frequently low, requiring a highly sensitive method of detection. Mouse bioassay is still the most used method of botulism identification from serum samples. However, in vitro methods based on BoNT endopeptidase activity with detection by mass spectrometry or immunoassay have been developed and depending on BoNT type, are more sensitive than the mouse bioassay. These new assays show high specificity for individual BoNT types and allow more accurate differentiation between positive toxin sera from botulism and autoimmune neuropathy patients. Full article
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