Treatment of interstitial cystitis

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.

What is claimed:  
     
         1 . A method for treating a disease associated with inhibited epithelial cell proliferation comprising administering an pharmaceutically effective amount of heparin binding epithelial growth factor (HB-EGF) or a functional derivative thereof.  
     
     
         2 . A method of    claim 1    wherein the epithelial cells are bladder cells.  
     
     
         3 . A method of    claim 1    wherein the disease is interstitial cystitis.  
     
     
         4 . A method of    claim 1    wherein the growth factor is recombinant HB-EGF.  
     
     
         5 . A method of    claim 2    wherein the growth factor is recombinant HB-EGF.  
     
     
         6 . A method of    claim 3    wherein the growth factor is recombinant HB-EGF.  
     
     
         7 . A method of    claim 1    wherein the step of administering step further comprises systemic administration.  
     
     
         8 . A method of    claim 7    wherein the systemic administration is selected from the group consisting of intravenous, subcutaneous, parenteral and oral.  
     
     
         9 . A method of    claim 1    wherein the step of administering step further comprises local administration.  
     
     
         10 . A method of    claim 9    wherein the local administration comprises topical administration.  
     
     
         11 . A method of    claim 9    wherein the local administration comprises intravesical administration.  
     
     
         12 . A method of claims  9 - 11  wherein the local administration takes the form of a liquid, a cream, an ointment, a suppository, or a gel.  
     
     
         13 . A method of    claim 1    wherein the step of administering step further comprises exogenous administration.  
     
     
         14 . A method of    claim 1    wherein the step of administering step further comprises endogenous administration.  
     
     
         15 . A method of    claim 14    wherein the endogenous administration comprises gene therapy to stimulate the local production of HB-EGF by the epithelial cells.  
     
     
         16 . A method of    claim 15    wherein the gene therapy involves viral vectors or bacterial vectors.  
     
     
         17 . A method of    claim 13    wherein the exogenous administration comprises an implantable dynamic system capable of continuously administering HB-EGF to the cells.  
     
     
         18 . The method of    claim 1    wherein said derivative of heparin binding epithelial growth factor (HB-EGF) is selected from the group consisting of anti-idiotypic antibodies to HB-EGF, fragments, variants of HB-EGF, analogues of HB-EGF, or chemical derivatives of HB-EGF.  
     
     
         19 . A method for treating a disease associated with inhibited epithelial cell proliferation comprising administering an pharmaceutically effective amount of an agonist of heparin binding epithelial growth factor (HB-EGF).