Method of treating interstitial cytitis with recombinant heparin-binding epidermal growth factor-like growth factor (hb-egf)

Abstract

Interstitial cystitis (IC) is a chronic bladder disease for which the exact etiology is unknown and for which there is no reliably effective treatment. However, it is known that the bladder epithelium is often abnormal in IC. We discovered that human bladder epithelial cells from both normal controls and IC patients are inhibited from proliferating by an anti-proliferative factor (APF) present in IC urine specimens. Inhibited proliferation may cause epithelial abnormalities characteristic of IC such as ulcerations and multiple tears in the bladder epithelium. We further discovered that 1) levels of heparin binding-epidermal growth factor-like growth factor (HB-EGF), a factor known be important for epithelial cell proliferation and wound healing in other tissues, are abnormally low in the urine of patients suffering from IC as compared to asymptomatic controls or patients with acute bacterial cystitis; 2) the APF found in IC urine specimens inhibits HB-EGF production by bladder epithelial cells; and 3) that the administration of rHB-EGF blocks the effects of APF on bladder epithelial cells from either IC patients or controls. The invention herein is directed to the administration of HB-EGF, or a functional derivative or agonist thereof, to bladder epithelial cells to inhibit the effects of APF on bladder cell proliferation, thereby reducing or eliminating the chronic damage to the bladder epithelium. HB-EGF or a functional derivative may be used as a therapy for patients suffering from IC or other diseases characterized by inhibited epithelial cell proliferation.