title: 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: OBJECTIVE
  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.
  
  
  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.affiliation: PhD Program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan; Voiding Dysfunction Therapeutic Center, Department of Medical Research, Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Hsin-Tzu
authors.initials: HT
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Tzu Chi University, Hualien, Taiwan.
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Department of Urology, William Beaumont Hospital Research Institute, Oakland University William Beaumont School of Medicine, Royal Oak, Michigan, United States of America.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Chancellor
authors.affiliation: Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.
authors.forename: Hann-Chorng
authors.initials: HC
authors.lastname: Kuo
mesh_terms: D000283:Administration, Intravesical; D001706:Biopsy; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004337:Drug Carriers; D015870:Gene Expression; D006801:Humans; D008081:Liposomes; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D058477:Receptors, Purinergic P2X3 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D012189:Retrospective Studies; D050825:Synaptosomal-Associated Protein 25 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000378:metabolism; D019459:Urothelium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D058477:Receptors, Purinergic P2X3; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25; C076414:SV2A protein, human; D019274:Botulinum Toxins, Type A; C545476:incobotulinumtoxinA