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Special Issue "Botulinum Neurotoxins and Nervous System: Future Challenges for Novel Indications"

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

Deadline for manuscript submissions: 31 March 2018

Special Issue Editor

Guest Editor
Dr. Siro Luvisetto

National Research Council (CNR) of Italy, Institute of Cell Biology and Neurobiology, Monterotondo Scalo, Roma 00015, Italy
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Special Issue Information

Dear Colleagues,

Botulinum toxins (BoNTs) are a true wonder of nature. Like Dr. Jekyll and Mr Hide, they have a double "personality" that makes them unique among toxins of bacterial origin. On the one hand, BoNTs are key components of several widely-used drugs, approved for a variety of clinical conditions, difficult to treat with other medicine. On the other hand, BoNTs are the causal agent of botulism and, with its highest toxicity among natural products, are one of the most dangerous bioterrorism agents. Both animal and clinical studies have extensively investigated the therapeutics effects for BoNTs, evidencing a variety of apparently different mechanisms which have in common the block of the cholinergic transmission at the neuromuscular junction. This discovery gave an extraordinary consensus to the clinical use of BoNTs in human pathologies characterized by excessive muscle contractions, i.e., the hypercholinergic dysfunctions going from torticollis, blepharospasms, dystonias, and so on. In recent years, a number of studies have provided evidence for the efficacy of BoNTs in alleviating human pain, including pain disorders associated with migraine. The list of human disorders in which treatments with BoNTs have produced, or are expected to produce, favorable results is long and continuously growing. This Special Issue “Botulinum Neurotoxins in Nervous System: Future Challenges for Novel Indications” is particularly devoted to collecting the most recent research on the effects of BoNTs in all cases where the expected therapeutic action is not attributable only to the its canonical mechanism, but also to the interaction of the toxins with other structures, including peripheral nerves, spinal cord, central neurons, non-neural cells, and so on. Both review and research articles are welcome, not only on animal studies, but also on clinical reports. The ambitious purpose of this Special Issue is to provide an up-to-date picture of the state-of-the-art on the possible development of novel BoNT applications for future therapeutic indications.

Dr. Siro Luvisetto
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • Botulinum
  • Peripheral nervous system
  • Central nervous system
  • Sensory motor system
  • Nerve regeneration
  • Spinal cord
  • Glial cells
  • Animal models
  • Clinical studies

Published Papers (1 paper)

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Open AccessFeature PaperReview Botulinum Toxin in Management of Limb Tremor
Toxins 2017, 9(11), 365; doi:10.3390/toxins9110365
Received: 24 October 2017 / Revised: 7 November 2017 / Accepted: 8 November 2017 / Published: 10 November 2017
PDF Full-text (214 KB) | HTML Full-text | XML Full-text
Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one’s ability to perform daily tasks becomes impaired. Oral
[...] Read more.
Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one’s ability to perform daily tasks becomes impaired. Oral therapies, including propranolol and primidone, can be effective in the management of essential tremor, although adverse effects can limit their use and about 50% of individuals lack response to oral pharmacotherapy. Locally administered botulinum toxin injection has become increasingly useful in the management of essential tremor. Targeting of select muscles with botulinum toxin is an area of active research, and muscle selection has important implications for toxin dosing and functional outcomes. The use of anatomical landmarks with palpation, EMG guidance, electrical stimulation, and ultrasound has been studied as a technique for muscle localization in toxin injection. Earlier studies implemented a standard protocol for the injection of (predominantly) wrist flexors and extensors using palpation and EMG guidance. Targeting of muscles by selection of specific activators of tremor (tailored to each patient) using kinematic analysis might allow for improvement in efficacy, including functional outcomes. It is this individualized muscle selection and toxin dosing (requiring injection within various sites of a single muscle) that has allowed for success in the management of tremors. Full article

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

1. Title: Antipruritic effects of botulinum neurotoxins

Author: Parisa Gazerani
Abstract: This review would explore current evidence to demonstrate that botulinum neurotoxins exert antipruritic effects. Both experimental and clinical conditions in which botulinum neurotoxins have been applied for itch relieving effects will be presented and significant findings will be highlighted. Potential mechanisms underlying antipruritic effects will also be discussed and ongoing challenges and unmet needs will be listed.
2. Title: Exploiting Botulinum neurotoxins for the study of brain pathologies
Matteo Caleo and Laura Restani
Abstract: Botulinum neurotoxins are metalloproteases that specifically cleave SNARE proteins in synaptic terminals, resulting in a potent inhibition of vesicle fusion and transmitter release. The family comprises different serotypes (BoNT/A to /G). The natural target of these toxins is represented by the neuromuscular junction, where BoNTs block acetylcholine release. In this review, we describe the actions of botulinum toxins after direct delivery to the central nervous system (CNS), where BoNTs block exocytosis of several transmitters at central synapses, with near-complete silencing of neural networks. The use of clostridial neurotoxins in the CNS has allowed to investigate specifically the role of synaptic activity in several physiological and pathological processes. The silencing properties of BoNTs can be exploited for for therapeutic purposes, for example to counteract pathological hyperactivity and seizures in epileptogenic brain foci, or to investigate the role of activity in degenerative diseases like prion disease. Altogether, clostridial neurotoxins and their derivatives hold promise as powerful tools for both the basic understanding of brain function and the dissection and treatment of activity-dependent pathogenic pathways.
3. Title: Botulinum neurotoxin and neurorehabilitation: state of the art and future perspectives

Authors: Stefano Tamburin, Giorgio Sandrini and collaborators

Abstract: Botulinum neurotoxin (BoNT) is widely used for the treatment of excessive and/or undesired muscle tone, in particular spasticity and dystonia and its therapeutic indications have progressively expanded. BoNT was recently licensed for chronic migraine, and represents an emerging treatment for an increasing number of pain conditions, including primary headache, trigeminal neuralgia, and neuropathic pain. BoNT is also used to treat bladder dysfunction.
Patients with neurological diseases undergoing neurorehabilitation often have more than one conditions (e.g. patients with spinal cord injury are frequently affected by spasticity, central neuropathic pain, and bladder dysfunction), and thanks to its wide therapeutic effects may target more than one problem with limited or no side effects.
The association of an ad hoc rehabilitative program may improve the efficacy of BoNT in several clinical conditions (e.g., dystonia).
Here we will review the role of BoNT in the field of neurorehabilitation, and future areas of focus for clinical research, such as potential role of BoNT injection therapy in combination with systemic drugs and/or physical therapies.
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