MP72-17 EFFECT OF AQX-1125 ON URINARY BLADDER INFLAMMATION AND PAIN INDUCED BY CYCLOPHOSPHAMIDE IN RATS, BY TARGETING THE SHIP1 PATHWAY

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis1 Apr 2016MP72-17 EFFECT OF AQX-1125 ON URINARY BLADDER INFLAMMATION AND PAIN INDUCED BY CYCLOPHOSPHAMIDE IN RATS, BY TARGETING THE SHIP1 PATHWAY Jennifer Cross, Curtis Harwig, Pat Tam, Judy Toews, and Lloyd Mackenzie Jennifer CrossJennifer Cross More articles by this author , Curtis HarwigCurtis Harwig More articles by this author , Pat TamPat Tam More articles by this author , Judy ToewsJudy Toews More articles by this author , and Lloyd MackenzieLloyd Mackenzie More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1630AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory syndrome characterized by pain, pressure or discomfort in the bladder and accompanied by urinary symptoms of frequency and urgency. AQX-1125, a novel SH2-containing inositol-5’-phosphatase 1 (SHIP1) activator with broad anti-inflammatory properties, represents a potential once-daily, oral therapy for IC/BPS. In rats, a single injection of cyclophosphamide (CYP) induces a chemical cystitis with similar features of IC/BPS, including inflammation of the bladder, visceral pain and an increase in urinary frequency. The aim of this study was to evaluate the effect of AQX-1125 (0.3, 3 and 30 mg/kg doses) on visceral pain, inflammation and cystometric parameters in acute CYP-induced cystitis in rats. METHODS Cystitis was induced in female Sprague Dawley rats by a single intraperitoneal injection (150 mg/kg) of CYP. For cystitis studies, AQX-1125 was administered once-daily for four, with the final dose given two hours prior to CYP challenge. Von Frey testing measured visceral pain at 4 hours post-challenge and bladders were excised to measure bladder wall thickness, cytokine levels and to score the extent of edema and hemorrhage. For cystometry studies, AQX-1125 was dosed five times at 30 mg/kg and urodynamic function was assessed at 48 hours post-CYP administration. RESULTS AQX-1125, at 0.3, 3 and 30 mg/kg, reduced visceral pain, assessed from von Frey 1-60 g, with maximal inhibitions occurring in the 1-6 g range (49%, 95% and 92%, respectively, as compared to the CYP/vehicle group). The AQX-1125 reduction in visceral pain (von Frey 1-60 g), was the same at 3 and 30 mg/kg (31%), and was comparable to the reference standard ibuprofen (37% at 300 mg/kg). AQX-1125 at 3 mg/kg also significantly decreased the inflammatory parameters of bladder wall thickness and the edema score. At 30 mg/kg, AQX-1125 also showed a positive trend in decreasing the intercontraction interval, evaluated during cystometry. CONCLUSIONS The novel SHIP1 activator, AQX-1125 is able to decrease visceral pain and bladder inflammation in a rodent model of cystitis. This compelling data supports development of AQX-1125 as an oral, once-daily therapy for IC/BPS. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e958 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Jennifer Cross More articles by this author Curtis Harwig More articles by this author Pat Tam More articles by this author Judy Toews More articles by this author Lloyd Mackenzie More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...