Presence of Cleaved Synaptosomal-Associated Protein-25 and Decrease of Purinergic Receptors P2X3 in the Bladder Urothelium Influence Efficacy of Botulinum Toxin Treatment for Overactive Bladder Syndrome

PLoS One. 2015 Aug 4;10(8):e0134803. doi: 10.1371/journal.pone.0134803. eCollection 2015.

Abstract

Objectives: To evaluate whether botulinum toxin A (BoNT-A) injection and Lipotoxin (liposomes with 200 U of BoNT-A) instillation target different proteins, including P2X3, synaptic vesicle glycoprotein 2A, and SNAP-25, in the bladder mucosa, leading to different treatment outcomes.

Materials and methods: This was a retrospective study performed in a tertiary teaching hospital. We evaluated the clinical results of 27 OAB patients treated with intravesical BoNT-A injection (n = 16) or Lipotoxin instillation (n = 11). Seven controls were treated with saline. Patients were injected with 100 U of BoNT-A or Lipotoxinin a single intravesical instillation. The patients enrolled in this study all had bladder biopsies performed at baseline and one month after BoNT-A therapy. Treatment outcome was measured by the decreases in urgency and frequency episodes at 1 month. The functional protein expressions in the urothelium were measured at baseline and after 1 month. The Wilcoxon signed-rank test and ordinal logistic regression were used to compare the treatment outcomes.

Results: Both BoNT-A injection and Lipotoxin instillation treatments effectively decreased the frequency of urgency episodes in OAB patients. Lipotoxin instillation did not increase post-void residual volume. BoNT-A injection effectively cleaved SNAP-25 (p < 0.01). Liposome encapsulated BoNT-A decreased urothelial P2X3 expression in the five responders (p = 0.04), while SNAP-25 was not significantly cleaved.

Conclusions: The results of this study provide a possible mechanism for the therapeutic effects of BoNT-A for the treatment of OAB via different treatment forms. BoNT-A and Lipotoxin treatments effectively decreased the frequency of urgency episodes in patients with OAB.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravesical
  • Biopsy
  • Botulinum Toxins, Type A / administration & dosage
  • Botulinum Toxins, Type A / pharmacology
  • Botulinum Toxins, Type A / therapeutic use*
  • Drug Carriers
  • Gene Expression
  • Humans
  • Liposomes
  • Membrane Glycoproteins / drug effects
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Receptors, Purinergic P2X3 / drug effects
  • Receptors, Purinergic P2X3 / genetics
  • Receptors, Purinergic P2X3 / physiology
  • Retrospective Studies
  • Synaptosomal-Associated Protein 25 / drug effects
  • Synaptosomal-Associated Protein 25 / genetics
  • Synaptosomal-Associated Protein 25 / metabolism
  • Treatment Outcome
  • Urinary Bladder / drug effects*
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urinary Bladder, Overactive / drug therapy*
  • Urinary Bladder, Overactive / metabolism
  • Urothelium / drug effects*
  • Urothelium / metabolism
  • Urothelium / pathology

Substances

  • Drug Carriers
  • Liposomes
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Receptors, Purinergic P2X3
  • SNAP25 protein, human
  • Synaptosomal-Associated Protein 25
  • SV2A protein, human
  • Botulinum Toxins, Type A
  • incobotulinumtoxinA

Grants and funding

This study was supported by grands from Buddhist Tzu Chi General Hospital (TCRD-19901-02) and the National Science Council of Taiwan (NSC 101-2314-B-303-003-MY3). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.