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.

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.

• Authors: Hsin-Tzu Liu, Sung-Ho Chen, Michael B Chancellor, Hann-Chorng Kuo
• Journal: PloS one (PLoS One) Vol. 10 Issue 8 Pg. e0134803 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26241848 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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