Research on Botulinum Toxin for Urinary System Diseases and Pelvic Pain

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 2810

Special Issue Editors

Neuro-urology unit, Department of Neuroscience, University Hospital Lausanne, UNIL, Lausanne Suisse
Interests: neuro-urology; functional urology
Neuro-Urology and Andrology Unit, Department of Physical Medecine and Rehabilitation, Hôpital Raymond Poincaré, APHP, Université Paris Saclay, Garches, France

Special Issue Information

Dear Colleagues,

The main medical innovation in recent years in neurogenic detrusor overactivity (NDO) and overactive bladder (OAB) has been the approval of intradetrusor onabotulinum toxin A.

While onabotulinum toxin A has been approved by FDA and EMA in 2011 for NDO and in 2014 for OAB, recent phase 2 RCTs have suggested that intradetrusor injections of botulinum toxin may also be effective in improving bladder pain syndrome/interstitial cystitis (BPS/IC), likely by reducing central and peripheral nerve sensitization, decreasing noxious neurotransmitter release, and targeting neurogenic inflammation. Despite the mainstream use of BonTA worldwide in treating NDO and OAB as well as BPS and/IC, the exact mechanisms of action are not fully understood. Moreover, there is still a lack in definition of failure of botulinum toxin intra-detrusor injections for NDO. There is still also a need to find a universal consensus for the management of NDO refractory to botulinum toxin.

There is also emerging evidence that in some neurogenic populations with NDO, that are non-using or not willing to have intermittent catheterization like multiple sclerosis or Parkinson patients, the ideal applied doses might not be the same as in other neurogenic populations, like SCI patients.

At least there are emerging indications on the use of botulinum toxin in urology-like refractory erectile dysfunction.

The aim of this Special Issue is to present a collection of articles by pioneers in the actual knowledge on the use of botulinum toxin in urology, known and possible mechanisms of action, and to describe their trials and drawbacks. This Special Issue also aims to describe the use of other botulinum toxin A and new developments in the administration route of the urological field.

Topics of interest include (but are not limited to):

  • Mechanism of action in OAB, NDO, BPS/IC
  • Therapy failure
  • New indication
  • New route of administration

We look forward to receiving your contributions.

Prof. Brigitte Schurch
Prof. Dr. Pierre Denys
Guest Editors

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Keywords

  • onabotulinum toxin
  • abobotulinum toxin
  • mechanisms of action
  • NDO
  • OAB
  • BPS/IC
  • therapy failure
  • multiple sclerosis
  • Parkinson
  • erectile dysfunction

Published Papers (1 paper)

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Research

11 pages, 1807 KiB  
Article
BoNT/A1 Secondary Failure for the Treatment of Neurogenic Detrusor Overactivity: An Ex Vivo Functional Study
by Jacquie Maignel, Vincent Martin, Rana Assaly, Mathieu L. Vogt, Kevin Retailleau, Fraser Hornby, Alexandra Laugerotte, Stéphane Lezmi, Pierre Denys, Johannes Krupp and Charles Joussain
Toxins 2022, 14(2), 77; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins14020077 - 21 Jan 2022
Viewed by 2416
Abstract
Management of neurogenic detrusor overactivity (NDO) remains a clinical priority to improve patients’ quality of life and prevent dramatic urological complications. Intradetrusor injection of onabotulinumtoxinA (BoNT/A1, botulinum neurotoxin A1) is approved as second therapeutic line in these patients, demonstrating a good efficacy. However, [...] Read more.
Management of neurogenic detrusor overactivity (NDO) remains a clinical priority to improve patients’ quality of life and prevent dramatic urological complications. Intradetrusor injection of onabotulinumtoxinA (BoNT/A1, botulinum neurotoxin A1) is approved as second therapeutic line in these patients, demonstrating a good efficacy. However, a loss of its efficacy over time has been described, with no clear understanding of the underlying mechanisms. This paper aims at shedding new light on BoNT/A1 secondary failure in NDO through functional and structural analysis. Three groups of patients (either non-NDO, NDO with no toxin history or toxin secondary failure) were investigated using an ex vivo bladder strip assay. Detrusor strips were tensed in organ baths and submitted to electrical field stimulation to generate contractions. Recombinant BoNT/A1 was then added at various concentrations and contractions recorded for 4 h. Histology exploring BoNT/A1 targets, fibrosis and neuronal markers was also used. Detrusor strips from patients with BoNT/A1 secondary failure displayed a smaller sensitivity to toxin ex vivo at 3 nM compared to the other groups. Histological evaluation demonstrated the presence of cleaved Synaptosomal-Associated Protein, 25 kDa (c-SNAP25) in the detrusor from the toxin-secondary failure population, indicating some remaining in vivo sensitivity to BoNT/A1 despite the therapeutic escape. Moreover, residual c-SNAP25 did not affect parasympathetic-driven contractions observed ex vivo. This study confirms the slightly lower efficacy of BoNT/A1 in the BoNT/A1 secondary failure NDO group, suggesting that the escape from BoNT/A1 efficacy in NDO occurs at least at the parasympathetic level and could imply compensatory mechanisms for detrusor contraction. Full article
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