Decrease in bladder overactivity with REN1820 in rats with cyclophosphamide induced cystitis

Purpose: Studies suggest that nerve growth factor (NGF) contributes to bladder overactivity stemming from bladder inflammation. Studies were performed to determine the NGF dependence of cyclophosphamide (CYP) induced changes in bladder function using the recombinant NGF sequestering protein REN1820. Materials and Methods: Urodynamic testing and behavioral observations were made in female rats treated with CYP (4 or 48 hours) and REN1820 or vehicle. Results: Rats examined 4 or 48 hours after CYP treatment plus REN1820 showed significantly fewer nonvoiding contractions with smaller amplitude (pless than or equal to0.01). Rats examined 48 hours after CYP treatment plus REN1820 showed decreased voiding frequency (pless than or equal to0.01). No changes in filling, threshold or micturition pressure were observed with REN1820 treatment. Rats treated with CYP plus REN1820 showed greater mobility and normal resting postures compared with rats treated with CYP plus vehicle. Conclusions: These studies demonstrate that the use of the NGF sequestering protein REN1820 in rats with CYP induced cystitis decreases bladder overactivity. This is characterized by 1) a decrease in the number and amplitude of nonvoiding contractions and 2) decreased voiding frequency. Rats treated with REN1820 showed greater mobility and normal resting postures, which may reflect improved overall health or well-being. REN1820 may prove to be a novel therapeutic in individuals with the chronic inflammatory bladder syndrome interstitial cystitis.