Special Issue "Botulinum Neurotoxin and Parkinson’s Disease"

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

Deadline for manuscript submissions: 31 December 2021.

Special Issue Editors

Prof. Dr. Andreas Wree
E-Mail Website
Guest Editor
Institute of Anatomy, Rostock University Medical Center, Gertrudenstrasse 9, 18057 Rostock, Germany
Interests: botulinum-neurotoxin; receptors; imaging; animal models of neurodegenerative diseases
Special Issues and Collections in MDPI journals
Dr. Veronica Alexandra Antipova
E-Mail Website
Guest Editor
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Macroscopic and Clinical Anatomy, Medical University of Graz, A-8010 Graz, Austria
Interests: botulinum neurotoxin; brain; neurodegenerative disease; animal models of neurodegenerative diseases; parkinson disease; huntington disease; behavior; receptors; morphometry

Special Issue Information

Dear Colleagues,

Parkinson’s disease (PD) is a progressive neurodegenerative disease, and is the second most frequently occurring of this type. The main motor symptoms of PD, such as bradykinesia, akinesia, rest tremor, rigidity, postural instability, and gait disorders, are caused by axonal degeneration of dopaminergic fibers in the striatum and subsequent or parallel loss of dopaminergic neurons in the substantia nigra pars compacta. In addition to these motor symptoms, patients with PD often experience non-motor symptoms, including autonomic dysfunction, olfactory deficits, cognitive decline, sleep disorders, and neuropsychiatric symptoms such as depression, anxiety, and psychosis.

The non-motor symptoms often appear years before the motor symptoms are first noticed, but they can become major problems for the patients and adversely affect quality of life. Medications used to treat both motor and non-motor symptoms in PD are often inadequately effective and can cause intolerable side effects.

Botulinum toxins, produced by the anaerobic bacterium Clostridium botulinum, are among the most potent poisons present in nature. They inhibit the release of acetylcholine from the presynaptic terminal by affecting SNARE and SNAP proteins. In recent years botulinum neurotoxin (BoNT) has been used for the treatment over 100 different medical indications. Many of the symptoms for which BoNT has been found to be effective occur in a variety of neurological disorders. Especially in Parkinson’s disease, BoNT has been successfully applied to treat various motor symptoms (i.e., limb, cervical, pharyngeal, oromandibular dystonia and rigidity, bruxism, blepharospasm and lid apraxia, dysphagia, hand and jaw tremor, camptocormia, freezing of gait) and non-motor symptoms (i.e., drooling and sialorrhea, seborrhea, hyperhidrosis), gastroenterological symptoms including constipation and overactive bladder, gynecological disorders, pain, and so on.

In this Special Issue, we ask experts to contribute manuscripts that examine the current therapeutic indications and effectiveness of BoNT in PD or respective animal models.

Prof. Dr. Andreas Wree
Dr. Veronica Alexandra Antipova
Guest Editors

Manuscript Submission Information

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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 double-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 2400 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.

Keywords

  • Parkinson’s disease
  • botulinum neurotoxin
  • treatment of motor symptoms
  • treatment of non-motor symptoms
  • clinical studies
  • animal models
  • peripheral nervous system
  • central nervous system

Published Papers (3 papers)

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Research

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Article
Antidepressant-Like Properties of Intrastriatal Botulinum Neurotoxin-A Injection in a Unilateral 6-OHDA Rat Model of Parkinson’s Disease
Toxins 2021, 13(7), 505; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13070505 - 20 Jul 2021
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Abstract
Parkinson’s patients often suffer from depression and anxiety, for which there are no optimal treatments. Hemiparkinsonian (hemi-PD) rats were used to test whether intrastriatal Botulinum neurotoxin-A (BoNT-A) application could also have antidepressant-like properties in addition to the known improvement of motor performance. To [...] Read more.
Parkinson’s patients often suffer from depression and anxiety, for which there are no optimal treatments. Hemiparkinsonian (hemi-PD) rats were used to test whether intrastriatal Botulinum neurotoxin-A (BoNT-A) application could also have antidepressant-like properties in addition to the known improvement of motor performance. To quantify depression- and anxiety-like behavior, the forced swim test, tail suspension test, open field test, and elevated plus maze test were applied to hemi-PD rats injected with BoNT-A or vehicle. Furthermore, we correlated the results in the forced swim test, open field test, and elevated plus maze test with the rotational behavior induced by apomorphine and amphetamine. Hemi-PD rats did not show significant anxiety-like behavior as compared with Sham 6-OHDA- + Sham BoNT-A-injected as well as with non-injected rats. However, hemi-PD rats demonstrated increased depression-like behaviors compared with Sham- or non-injected rats; this was seen by increased struggling frequency and increased immobility frequency. Hemi-PD rats intrastriatally injected with BoNT-A exhibited reduced depression-like behavior compared with the respective vehicle-receiving hemi-PD animals. The significant effects of intrastriatally applied BoNT-A seen in the forced swim test are reminiscent of those found after various antidepressant drug therapies. Our data correspond with the efficacy of BoNT-A treatment of glabellar frown lines in treating patients with major depression and suggest that also intrastriatal injected BoNT-A may have some antidepressant-like effect on hemi-PD. Full article
(This article belongs to the Special Issue Botulinum Neurotoxin and Parkinson’s Disease)
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Review

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Review
Therapeutic Applications of Botulinum Neurotoxin for Autonomic Symptoms in Parkinson’s Disease: An Updated Review
Toxins 2021, 13(3), 226; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13030226 - 19 Mar 2021
Viewed by 754
Abstract
Parkinson’s disease is the most common age-related motoric neurodegenerative disease. In addition to the cardinal motor symptoms of tremor, rigidity, bradykinesia, and postural instability, there are numerous non-motor symptoms as well. Among the non-motor symptoms, autonomic nervous system dysfunction is common. Autonomic symptoms [...] Read more.
Parkinson’s disease is the most common age-related motoric neurodegenerative disease. In addition to the cardinal motor symptoms of tremor, rigidity, bradykinesia, and postural instability, there are numerous non-motor symptoms as well. Among the non-motor symptoms, autonomic nervous system dysfunction is common. Autonomic symptoms associated with Parkinson’s disease include sialorrhea, hyperhidrosis, gastrointestinal dysfunction, and urinary dysfunction. Botulinum neurotoxin has been shown to potentially improve these autonomic symptoms. In this review, the varied uses of botulinum neurotoxin for autonomic dysfunction in Parkinson’s disease are discussed. This review also includes discussion of some additional indications for the use of botulinum neurotoxin in Parkinson’s disease, including pain. Full article
(This article belongs to the Special Issue Botulinum Neurotoxin and Parkinson’s Disease)
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Review
Use of Botulinum Neurotoxin in Parkinson’s Disease: A Critical Appraisal
Toxins 2021, 13(2), 87; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13020087 - 25 Jan 2021
Viewed by 691
Abstract
For well over 30 years, the botulinum neurotoxin (BoNT) has been used for a large number of indications, some of which however have not been licensed. Admittedly, approval varies in many countries and this permits a large spectrum for evaluation. Thus, BoNT is [...] Read more.
For well over 30 years, the botulinum neurotoxin (BoNT) has been used for a large number of indications, some of which however have not been licensed. Admittedly, approval varies in many countries and this permits a large spectrum for evaluation. Thus, BoNT is used for patients with Parkinson’s disease (PD) and other Parkinson’s syndromes (PS) in varying degrees of frequency. We have to distinguish between (1) indications that are either approved or (2) those not approved, (3) indications that might be a result of PS and (4) finally those which appear independent of PS. The most important indication for BoNT in PS patients is probably sialorrhea, for which approval has been granted in the majority of countries. Cervical dystonia is a frequent symptom in PS, with anterocollis as a specific entity. A further indication is blepharospasm in the different forms, especially the inhibition of eyelid opening in atypical PS. The use of BoNT in cases of camptocormia, the Pisa syndrome and neck rigidity is still a matter of debate. In dystonia of the extremities BoNT can be recommended, especially in dystonia of the feet. One well-known indication, for which however sufficient data are still lacking, involves treating tremor with BoNT. As to autonomic symptoms: Focal hyperhidrosis and detrusor hyperactivity can be mentioned, in this last case BoNT has already been approved. A number of further but rare indications such as freezing-of-gait, dyskinesia, and dysphagia will be discussed and evaluated. Full article
(This article belongs to the Special Issue Botulinum Neurotoxin and Parkinson’s Disease)
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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.

Title: Use of Botulinum Neurotoxin in Parkinson’s Disease
Authors: Wolfgang H. Jost, Parkinson-Klinik Ortenau, Wolfach
Affiliation: Parkinson-Klinik Ortenau GmbH & Co KG Kreuzbergstr. 12-16 77709 Wolfach
Abstract: For well over 30 years botulinum neurotoxin (BoNT) has been used for a large number of indications, some of which however have not been approved. Admittedly, approval varies in many countries and this permits a large spectrum for evaluation. And thus BoNT is used for patients with Parkinson’s disease (PD) and other Parkinson’s syndromes (PS) in varying degrees of frequency. We have to distinguish between (1) indications that are either approved or (2) not approved, (3) those that might be present with PS and (4) finally those which do appear due to PS. The most important indication for BoNT in PS-patients is probably sialorrhea, for which approval has been granted in the majority of countries. Cervical dystonia is a frequent symptom in PS, with anterocollis in aPS as a special entity. A further indication is blephorospasmus which all the different forms, especially the inhibition of eye-lid opening in aPS. The use of BoNT in cases of camptocormia, the Pisa syndrome and neck rigidity, is still a matter of debate. In dystonia of the extremities BoNT can be recommended, especially in dystonia of the feet. One well-known indication for which however sufficient data are still lacking involves treating tremor with BoNT. As to autonomic symptomes, focal hyperhidrosis and detrusor hyperactivity can be mentioned, in this last case it has already been approved. A number of further but rare indications like freezing-of-gait, dyskinesia, and dysphagia will be discussed and evaluated.

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