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Toxins
Special Issues
Clinical Applications and Diversity of Botulinum Toxins
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Clinical Applications and Diversity of Botulinum Toxins

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

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 20668

Special Issue Editor

Dr. Christine Rasetti-Escargueil

E-Mail Website
Guest Editor
Institut Pasteur, Unité des Bactéries Anaérobies et Toxines, 25 Avenue du Docteur Roux, 75015 Paris, France
Interests: botulism; botulinum neurotoxins; antitoxins
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Botulinum neurotoxins (BoNTs) are produced by Gram-positive, anaerobic and spore-forming bacteria belonging to the genus Clostridium (Clostridium botulinum, C. butyricum, C. baratii and C. argentinense spp), with high immunological and genetic diversity. BoNTs are divided into nine toxinotypes (A, B, C, D, E, F, G, H or F/A, X) based on serological methods using specific antisera or, more recently, using genome sequencing for BoNT/X. To add further complexity, each toxinotype is subdivided into subtypes based on amino acid variations, leading to the identification of 41 subtypes so far. BoNTs are classified as the most harmful biological weapons due to their extreme potency. At the same time, BoNTs are widely used in therapy for an increasing number of applications. Enhancing our understanding of the activity of the BoNT variants, as well as the development of BoNT-based engineered proteins, opens the door to novel applications. Moreover, there is a pressing need to optimize the current detection methods challenged by BoNT diversity. This review will focus on BoNTs’ variability and the opportunities or challenges posed for future clinical applications.

Dr. Christine Rasetti-Escargueil
Guest Editor

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Keywords

  • botulinum neurotoxins (BoNTs)
  • subtypes
  • BoNT variants
  • detection
  • antitoxins

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Published Papers (6 papers)

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Research

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11 pages, 1576 KiB  
Article
Pain Control during the Treatment of Primary Palmar Hyperhidrosis with Botulinum Toxin A by a Topical Application of Liposomal Lidocaine: Clinical Effectiveness
by Andrea Marani, Helena Gioacchini, Matteo Paolinelli, Ivan Bobyr, Emanuela Martina, Giulia Radi, Federico Diotalallevi and Anna Campanati
Toxins 2024, 16(1), 28; https://doi.org/10.3390/toxins16010028 - 6 Jan 2024
Cited by 2 | Viewed by 3228
Abstract
Primary palmar hyperhidrosis (PPH) constitutes a debilitating condition that profoundly impacts the social, functional, and occupational aspects of individuals. The intradermal administration of botulinum toxin type A (BoNT-A) stands as an established therapeutic approach for PPH, albeit one frequently accompanied by considerable pain, [...] Read more.
Primary palmar hyperhidrosis (PPH) constitutes a debilitating condition that profoundly impacts the social, functional, and occupational aspects of individuals. The intradermal administration of botulinum toxin type A (BoNT-A) stands as an established therapeutic approach for PPH, albeit one frequently accompanied by considerable pain, posing challenges for patient tolerance. Our study aimed to assess the efficacy of combining cryoanalgesia spray (CA) with topical anesthesia utilizing a cream containing liposomal lidocaine at a concentration of 40 mg/g, with the objective of mitigating the pain associated with intradermal BoNT-A injection for PPH treatment. Nineteen participants, aged ≥18 years and afflicted with severe PPH, were enrolled in a double-blind randomized vehicle-controlled trial. Patient-perceived pain during the procedure was quantified using the Numeric Rating Scale (NRS). Statistical analysis was applied to the collected data. The combination of CA and the topical application of liposomal lidocaine during BoNT-A treatment for PPH resulted in diminished pain compared to CA alone and the combination of CA with the application of a basic cream. Topical anesthesia through the application of a liposomal lidocaine-containing cream emerged as a facile, secure, and efficacious approach for alleviating the pain associated with intradermal BoNT-A injection in PPH treatment. Furthermore, it demonstrated compatibility with CA, thereby offering a comprehensive strategy for pain management during BoNT-A administration. Full article
(This article belongs to the Special Issue Clinical Applications and Diversity of Botulinum Toxins)
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14 pages, 2132 KiB  
Article
Efficacy of Botulinum Toxin Type A for Prevention of Post-Mastectomy Scar in Transmen: A Prospective, Randomized Study
by Waranaree Winayanuwattikun, Vasanop Vachiramon, Teerapong Rattananukrom, Pasita Palakornkitti and Ngamcherd Sitpahul
Toxins 2023, 15(11), 636; https://doi.org/10.3390/toxins15110636 - 31 Oct 2023
Cited by 4 | Viewed by 3073
Abstract
Background: Subcutaneous mastectomies in transmen have been gaining popularity. However, post-operative scars are an inevitable consequence. Recently, Botulinum neurotoxin A (BoNT-A) has shown positive effects in scar prevention. The objective of this study is to investigate the effectiveness of BoNT-A in scar prevention. [...] Read more.
Background: Subcutaneous mastectomies in transmen have been gaining popularity. However, post-operative scars are an inevitable consequence. Recently, Botulinum neurotoxin A (BoNT-A) has shown positive effects in scar prevention. The objective of this study is to investigate the effectiveness of BoNT-A in scar prevention. Methods: Fifteen patients who had undergone subcutaneous mastectomy were included. At 14 days post-surgery, either incoBoNT-A or a placebo was injected into the scar on each side. The primary outcome assessment measured the scar’s severity using the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). The secondary outcome assessment evaluated the scar’s color using a standard measurement device. Outcome assessments were conducted until 6 months post-surgery. Results: There were significantly lower VSS scores in the BoNT-A group compared to the placebo at the end of the study (7.43 ± 0.26 vs. 8.82 ± 0.26, p < 0.001). The objective assessment revealed a statistically significant decrease in redness values in the BoNT-A group compared to the placebo at 3 and 6 months. Conclusion: BoNT-A has demonstrated effectiveness in scar prevention by reducing the severity of postoperative scar formation and improving overall scar appearance. Full article
(This article belongs to the Special Issue Clinical Applications and Diversity of Botulinum Toxins)
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12 pages, 13432 KiB  
Article
Ideal Injection Points for Botulinum Neurotoxin for Pectoralis Minor Syndrome: A Cadaveric Study
by Ji-Hyun Lee, Hyung-Jin Lee, Kyu-Ho Yi, Kang-Woo Lee, Young-Chun Gil and Hee-Jin Kim
Toxins 2023, 15(10), 603; https://doi.org/10.3390/toxins15100603 - 7 Oct 2023
Cited by 1 | Viewed by 3957
Abstract
Pectoralis Minor Syndrome (PMS) causes significant discomfort due to the compression of the neurovascular bundle within the retropectoralis minor space. Botulinum neurotoxin (BoNT) injections have emerged as a potential treatment method; however, their effectiveness depends on accurately locating the injection site. In this [...] Read more.
Pectoralis Minor Syndrome (PMS) causes significant discomfort due to the compression of the neurovascular bundle within the retropectoralis minor space. Botulinum neurotoxin (BoNT) injections have emerged as a potential treatment method; however, their effectiveness depends on accurately locating the injection site. In this study, we aimed to identify optimal BoNT injection sites for PMS treatment. We used twenty-nine embalmed and eight non-embalmed human cadavers to determine the origin and intramuscular arborization of the pectoralis minor muscle (Pm) via manual dissection and Sihler’s nerve staining techniques. Our findings showed the Pm’s origin near an oblique line through the suprasternal notch, with most neural arborization within the proximal three-fourths of the Pm. Blind dye injections validated these results, effectively targeting the primary neural arborized area of the Pm at the oblique line’s intersection with the second and third ribs. We propose BoNT injections at the arborized region within the Pm’s proximal three-fourths, or the C region, for PMS treatment. These findings guide clinicians towards safer, more effective BoNT injections. Full article
(This article belongs to the Special Issue Clinical Applications and Diversity of Botulinum Toxins)
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Review

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29 pages, 703 KiB  
Review
Embracing the Versatility of Botulinum Neurotoxins in Conventional and New Therapeutic Applications
by Christine Rasetti-Escargueil and Stefano Palea
Toxins 2024, 16(6), 261; https://doi.org/10.3390/toxins16060261 - 4 Jun 2024
Cited by 4 | Viewed by 4555
Abstract
Botulinum neurotoxins (BoNTs) have been used for almost half a century in the treatment of excessive muscle contractility. BoNTs are routinely used to treat movement disorders such as cervical dystonia, spastic conditions, blepharospasm, and hyperhidrosis, as well as for cosmetic purposes. In addition [...] Read more.
Botulinum neurotoxins (BoNTs) have been used for almost half a century in the treatment of excessive muscle contractility. BoNTs are routinely used to treat movement disorders such as cervical dystonia, spastic conditions, blepharospasm, and hyperhidrosis, as well as for cosmetic purposes. In addition to the conventional indications, the use of BoNTs to reduce pain has gained increased recognition, giving rise to an increasing number of indications in disorders associated with chronic pain. Furthermore, BoNT-derived formulations are benefiting a much wider range of patients suffering from overactive bladder, erectile dysfunction, arthropathy, neuropathic pain, and cancer. BoNTs are categorised into seven toxinotypes, two of which are in clinical use, and each toxinotype is divided into multiple subtypes. With the development of bioinformatic tools, new BoNT-like toxins have been identified in non-Clostridial organisms. In addition to the expanding indications of existing formulations, the rich variety of toxinotypes or subtypes in the wild-type BoNTs associated with new BoNT-like toxins expand the BoNT superfamily, forming the basis on which to develop new BoNT-based therapeutics as well as research tools. An overview of the diversity of the BoNT family along with their conventional therapeutic uses is presented in this review followed by the engineering and formulation opportunities opening avenues in therapy. Full article
(This article belongs to the Special Issue Clinical Applications and Diversity of Botulinum Toxins)
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13 pages, 1046 KiB  
Review
Recent Developments in Engineering Non-Paralytic Botulinum Molecules for Therapeutic Applications
by Aisha Zhantleuova, Charlotte Leese, Anna P. Andreou, Altynay Karimova, Guy Carpenter and Bazbek Davletov
Toxins 2024, 16(4), 175; https://doi.org/10.3390/toxins16040175 - 3 Apr 2024
Cited by 2 | Viewed by 2417
Abstract
This review discusses the expanding application of botulinum neurotoxin in treating neurological conditions. The article specifically explores novel approaches to using non-paralytic botulinum molecules. These new molecules, such as BiTox or el-iBoNT, offer an alternative for patients who face limitations in using paralytic [...] Read more.
This review discusses the expanding application of botulinum neurotoxin in treating neurological conditions. The article specifically explores novel approaches to using non-paralytic botulinum molecules. These new molecules, such as BiTox or el-iBoNT, offer an alternative for patients who face limitations in using paralytic forms of botulinum neurotoxin due to concerns about muscle function loss. We highlight the research findings that confirm not only the effectiveness of these molecules but also their reduced paralytic effect. We also discuss a potential cause for the diminished paralytic action of these molecules, specifically changes in the spatial parameters of the new botulinum molecules. In summary, this article reviews the current research that enhances our understanding of the application of new botulinum neurotoxins in the context of common conditions and suggests new avenues for developing more efficient molecules. Full article
(This article belongs to the Special Issue Clinical Applications and Diversity of Botulinum Toxins)
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19 pages, 498 KiB  
Review
Navigating the Complexities Involving the Identification of Botulinum Neurotoxins (BoNTs) and the Taxonomy of BoNT-Producing Clostridia
by Theresa J. Smith, Kristin M. Schill and Charles H. D. Williamson
Toxins 2023, 15(9), 545; https://doi.org/10.3390/toxins15090545 - 3 Sep 2023
Cited by 4 | Viewed by 2404
Abstract
Botulinum neurotoxins are a varied group of protein toxins that share similar structures and modes of activity. They include at least seven serotypes and over forty subtypes that are produced by seven different clostridial species. These bacterial species are not limited strictly to [...] Read more.
Botulinum neurotoxins are a varied group of protein toxins that share similar structures and modes of activity. They include at least seven serotypes and over forty subtypes that are produced by seven different clostridial species. These bacterial species are not limited strictly to BoNT-producers as neuro-toxigenic and non-neuro-toxigenic members have been identified within each species. The nomenclature surrounding these toxins and associated bacteria has been evolving as new isolations and discoveries have arisen, resulting in challenges in diagnostic reporting, epidemiology and food safety studies, and in the application of therapeutic products. An understanding of the intricacies regarding the nomenclature of BoNTs and BoNT-producing clostridia is crucial for communication that allows for accurate reporting of information that is pertinent to each situation. Full article
(This article belongs to the Special Issue Clinical Applications and Diversity of Botulinum Toxins)
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