In this editorial, he shares the research of a team in Oklahoma which has shown chondroitin, when used intravesically in rats, restores what appears to be normal bladder lining function. Fascinating. Of course, the use of chondroitin as a bladder instillation isn't new in IC circles. It's been used for years in a product called Uracyst, available in Canada and Europe. But this is a keen insight into it's potential. Watson Pharmaceuticals is in Phase III studies of a new chondroitin instillation for IC. - Jill O.

Editorial - Restoring barrier function to acid damaged bladder by intravesical chondroitin sulfate

Thursday, 03 December 2009 BERKELEY, CA (UroToday.com) -

Intravesical Chondroitin Sulfate Shows Potential Therapeutic Promise for BPS

It seems evident that in many cases, bladder pain syndrome pathophysiology may involve epithelial dysfunction. The bladder maintains a complex set of defenses comprising tight junction proteins and a dense glycosaminoglycan (GAG) layer on the specialized urothelial apical cells (umbrella cells). These defenses are presumably compromised in some BPS patients causing the urothelium to become “leaky”, resulting in the appearance of substances added intravesically into the circulation or reabsorption of fluorescein from urine. The GAG layer has been proposed to represent a major component of the impermeability barrier, though its importance can be questioned based on the variability of symptomatic results from GAG therapies taken orally or administered intravesically. Intravesical GAG therapy with sodium pentosan polysulfate, heparin or hyaluronic acid has not yet been proven efficacious in large, multicenter, randomized controlled trials.

An important publication by Paul Hauser and colleagues from Oklahoma City looked at the GAG chondroitin sulfate in an animal model to explore its possible applicability to therapy of BPS. Let me state at the outset of this report that I (Philip Hanno) have been a consultant for Watson Pharmaceuticals, a company currently testing intravesical chondroitin sulfate for BPS in phase 3 trials around the country.

The Oklahoma group, led by Robert Hurst, quantified chondroitin sulfate binding to normal and acid damaged mouse bladder over the range of pH values expected in urine. Chondroitin sulfate provides several potential advantages over heparin, sodium pentosanpolysulfate, and hyaluronan in simple barrier restoration. It has no effect on the coagulation system (although this has not been a problem with any intravesical treatment to date), it is inactive against many receptor systems that are affected by heparinoids and hyaluronan, and it is inexpensive.

Hauser and co-workers found that in a model of acid damaged rat bladder, intravesical chondroitin sulfate restored bladder impermeability to rubidium ions to control levels. 86Rubidium belongs to the same family of elements as potassium and is used as a model for potassium movement across membranes because of the impractically short half-life of potassium isotopes. They quantified the capacity of acid damaged bladder to intravesically adsorb applied chondroitin sulfate and found that this binding is saturable, supporting the intravesical dose of 400 mg used currently marketed in Canada for BPS intravesical therapy.

Chondroitin sulfate intravesical solution is currently in phase 3 testing in the US.

Hauser PJ, Buethe DA, Califano J, Sofinowski TM, Culkin DJ, Hurst RE

J Urol. 2009 Nov;182(5):2477-82 10.1016/j.juro.2009.07.013

(Reprinted with permission of Urotoday)