Glycosaminoglycan Therapy for Bladder Diseases: Emerging New Treatments

Abstract

Damage to the urothelial gycosaminoglycan (GAG) barrier layer is thought to underlie the pathogenesis of several chronic bladder pathologies, including interstitial cystitis/painful bladder syndrome (IC/PBS), chemical or radiation cystitis, and recurrent urinary tract infections (UTIs). Penetration of urinary constituents into the bladder wall causes C-fiber activation, mast cell activation, and histamine release. The resulting smooth muscle contraction, neurogenic inflammation, and hypersensitivity translate into the urinary urgency and frequency and chronic pelvic pain that are characteristic symptoms of several chronic bladder conditions. Protecting the urothelium or promptly restoring the GAG layer to prevent the cycle of inflammation and hypersensitization is the basis for the clinical use of intravesical instillations of sodium hyaluronate–chondroitin sulfate (HA-CS; Ialuril ®; IBSA Institut Biochimique SA, Lugano, Switzerland). In an experimental animal model, HA-CS instillations counteracted the increase of micturition frequency and threshold pressure, and they increased the bladder compliance, following urothelial damage induced by protamine sulfate and potassium chloride. In the clinical setting, patients with IC/PBS receiving intravesical HA-CS experienced significantly fewer micturitions, increased voiding volumes, symptomatic improvement with respect to pain and urgency/frequency symptom scores, and improved quality of life. In patients with recurrent UTIs, urinary intravesical HA-CS prompted an almost 90% reduction of episodes per patient per year versus 10% in the control group and, compared with the control group, patients in the HA-CS group lasted 3.5-fold longer between episodes. The potential role of intravesical HA-CS as GAG replacement therapy in other chronic and challenging bladder conditions, including overactive bladder, calculi, and urothelial cancer, is being investigated. Urothelial damage is the central theme of many chronic bladder pathologies. Intravesical instillation of the sodium hyaluronate 1.6%–chondroitin sulfate 2% combination has proved to be a useful treatment approach for the protection and replacement of this GAG barrier layer.