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Keywords = BITOX

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13 pages, 1046 KB  
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 7 | Viewed by 4021
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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11 pages, 349 KB  
Article
Re-Assembled Botulinum Neurotoxin Inhibits CNS Functions without Systemic Toxicity
by Enrico Ferrari, Elizabeth S. Maywood, Laura Restani, Matteo Caleo, Marco Pirazzini, Ornella Rossetto, Michael H. Hastings, Dhevahi Niranjan, Giampietro Schiavo and Bazbek Davletov
Toxins 2011, 3(4), 345-355; https://doi.org/10.3390/toxins3040345 - 24 Mar 2011
Cited by 34 | Viewed by 11274
Abstract
The therapeutic potential of botulinum neurotoxin type A (BoNT/A) has recently been widely recognized. BoNT/A acts to silence synaptic transmission via specific proteolytic cleavage of an essential neuronal protein, SNAP25. The advantages of BoNT/A-mediated synaptic silencing include very long duration, high potency and [...] Read more.
The therapeutic potential of botulinum neurotoxin type A (BoNT/A) has recently been widely recognized. BoNT/A acts to silence synaptic transmission via specific proteolytic cleavage of an essential neuronal protein, SNAP25. The advantages of BoNT/A-mediated synaptic silencing include very long duration, high potency and localized action. However, there is a fear of possible side-effects of BoNT/A due to its diffusible nature which may lead to neuromuscular blockade away from the injection site. We recently developed a “protein-stapling” technology which allows re-assembly of BoNT/A from two separate fragments. This technology allowed, for the first time, safe production of this popular neuronal silencing agent. Here we evaluated the re-assembled toxin in several CNS assays and assessed its systemic effects in an animal model. Our results show that the re-assembled toxin is potent in inhibiting CNS function at 1 nM concentration but surprisingly does not exhibit systemic toxicity after intraperitoneal injection even at 200 ng/kg dose. This shows that the re-assembled toxin represents a uniquely safe tool for neuroscience research and future medical applications. Full article
(This article belongs to the Special Issue Development of Botulinum Toxin Drugs)
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