Anti-PVR monoclonal antibody, clone CBSB035CB.

Introduction: Botulinum toxin A (BTX-A) is currently used as a fourth-line therapeutic option for interstitial cystitis/bladder pain syndrome (IC/BPS) management. The purpose of this study was to determine if BTX-A injection can mitigate pain and if injection location (i.e. trigone-including versus trigone-sparing injection template) impacts treatment efficacy and/or treatment complications profile. Materials and methods: Female IC/BPS patients refractory to conservative management strategies were prospectively enrolled and asked to complete a baseline history and physical exam, post-void residual (PVR) urine volume determination, O'Leary Sant (OLS) questionnaire, and Pelvic Pain and Urgency/Frequency Symptom Scale (PUF) questionnaire. Participants were randomly assigned to one of two treatment groups and received either: 1) a trigone-including BTX-A injection template or 2) a trigone-sparing injection template. Following therapy, patients were examined in clinic at 30 and 90 day post-treatment with symptom re-assessment via repeat questionnaires and for evidence of post-procedural complications. Results: Compared to baseline, patients in both treatment groups experienced significant improvement in OLS and PUF scores at both 30 and 90 days post-treatment with BTX-A, regardless of which injection template was used (p < 0.05). Complications resulting from BTX-A were minimal (most commonly urinary tract infection (UTI) and urinary retention) and not significantly different between the treatment groups (p > 0.05). No distant spread of BTX-A was observed in any patient in either treatment group. Conclusions: BTX-A treatment using either a trigone-sparing or trigone-including injection template resulted in significant, but not location-dependent, improvement in IC/BPS symptom scores at 30 and 90 day points post-procedure with no significant difference in post-treatment complication profiles.

Objective: To evaluate whether approved gastroprokinetic agent, acotiamide exerts a direct excitatory effect on bladder to help explain the reported meaningful reduction of post-void residual urine volume (PVR) in detrusor underactivity (DU) patients after thrice daily oral intake of acotiamide 100 mg for 2 weeks. Methods: Effect of acotiamide [1-16 mu M] was assessed on nerve-mediated contractions evoked by electrical field stimulation (EFS) for 5 s with 5 ms pulse trains of 10 V in longitudinal, mucosa intact rat and human bladder strips to construct frequency response curve (1-32 Hz) and repeat 10 Hz stimulation at 60s interval. Effect of acotiamide 2 mu M on spontaneous and carbachol evoked contractions was also assessed. Results: Acotiamide 2 mu M significantly enhanced the Atropine and Tetrodotoxin (ITX)-sensitive EFS evoked contractions of rat and human bladder at 8-32 Hz (Two-way ANOVA followed Sidak's multiple comparison; *p < 0.01) and on repeat 10 Hz stimulation (Paired Student's t-test; *p < 0.05), while producing a modest effect on the spontaneous contractions and a negligible effect on the carbachol evoked contractions. Conclusions: Enhancement of TTX-sensitive evoked contractions of rat and human bladder by acotiamide is consistent with the enhancement of excitatory neuro-effector transmission mainly through prejunctional mechanisms. Findings highlight immense therapeutic potential of antimuscarinics with low M3 receptor affinity like acotiamide in Underactive bladder (UAB)/DU treatment.