Treatment of endometriosis with antileukoprotease

Abstract

This invention provides methods for diagnosing and treating endometriosis, and promoting implantation of an embryo. The methods involve determining or modulating antileukoprotease activity in a subject.

What is claimed is:  
     
         1 . A method for the treatment of endometriosis in a subject comprising administering to the subject an amount of antileukoprotease effective to inhibit the activity of elastase or cathepsin G, thereby inhibiting ectopic implantation of endometrial fragments.  
     
     
         2 . The method of  claim 1  wherein the antileukoprotease is administered intraperitoneally or intravaginally.  
     
     
         3 . The method of  claim 1  wherein the antileukoprotease is administered in a pharmaceutical composition comprising an injectable aqueous solution.  
     
     
         4 . The method of  claim 1  wherein the antileukoprotease is administered by providing endometrial epithelial cells of the subject with an expression cassette comprising an expression control sequence operatively linked with a nucleotide sequence encoding antileukoprotease.  
     
     
         5 . A method comprising measuring an amount of antileukoprotease activity in an endometrial tissue sample from a subject.  
     
     
         6 . The method of  claim 5  wherein the endometrial tissue is eutopic endometrial tissue.  
     
     
         7 . The method of  claim 5  wherein the endometrial tissue is ectopic endometrial tissue.  
     
     
         8 . The method of  claim 5  wherein the amount of antileukoprotease is measured as a function of the amount of antileukoprotease mRNA in the sample.  
     
     
         9 . The method of  claim 5  wherein the amount of antileukoprotease is measured as a function of the amount of antileukoprotease activity in the sample.  
     
     
         10 . A method for diagnosing endometriosis comprising: 
 a) measuring a test amount of antileukoprotease activity in a eutopic endometrial tissue sample from a subject, and    b) comparing the test amount with a normal amount of antileukoprotease activity; 
 whereby a test amount above the normal amount provides a positive sign in a diagnosis of endometriosis.  
   
     
     
         11 . The method of  claim 10  wherein the amount of antileukoprotease is measured as a function of the amount of antileukoprotease mRNA in the sample.  
     
     
         12 . The method of  claim 10  wherein the amount of antileukoprotease is measured as a function of the amount of antileukoprotease activity in the sample.  
     
     
         13 . A method for diagnosing endometriosis comprising: 
 a) measuring a test amount of antileukoprotease activity in an ectopic endometrial tissue sample from a subject, and    b) comparing the test amount with a normal amount of antileukoprotease activity; 
 whereby a test amount below the normal amount provides a positive sign in a diagnosis of endometriosis.  
   
     
     
         14 . The method of  claim 13  wherein the amount of antileukoprotease is measured as a function of the amount of antileukoprotease mRNA in the sample.  
     
     
         15 . The method of  claim 13  wherein the amount of antileukoprotease is measured as a function of the amount of antileukoprotease activity in the sample.  
     
     
         16 . A method for diagnosing endometriosis comprising: 
 a) measuring a first test amount of antileukoprotease activity in an ectopic endometrial tissue sample from a subject,    b) measuring a second test amount of antileukoprotease activity in a eutopic endometrial tissue sample from a subject, and    c) determining a test difference between the first test amount and the second test amount;    d) comparing the test difference with a normal difference between amounts of antileukoprotease activity in ectopic and eutopic endometrial tissue;    whereby a test difference greater than a normal difference provides a positive sign in a diagnosis of endometriosis.    
     
     
         17 . Tile method of  claim 16  wherein the amount of antileukoprotease is measured as a function of the amount of antileukoprotease mRNA in the sample.  
     
     
         18 . The method of  claim 16  wherein the amount of antileukoprotease is measured as a function of the amount of antileukoprotease activity in the sample.  
     
     
         19 . The method of  claim 16  wherein the normal difference is a factor of fifteen.  
     
     
         20 . A method of facilitating implantation of an embryo in the uterus of a subject comprising administering to the subject, in early pregnancy or before conception, an effective amount of a compound that inhibits the activity of antileukoprotease.  
     
     
         21 . The method of  claim 20  comprising administering the compound intravaginally.  
     
     
         22 . A method for identifying a modulator of antileukoprotease activity comprising: 
 a) contacting a test compound which is not an elastase or cathepsin G modulator with antileukoprotease;    b) measuring an amount of antileukoprotease activity; and    c) determining whether the measured amount is different than a control amount of activity when antileukoprotease is not contacted with the agent;    whereby a measured amount different than a control amount identifies the compound as a modulator of antileukoprotease.    
     
     
         23 . The method of  claim 22  wherein measuring the amount of antileukoprotease activity comprises contacting antileukoprotease with elastin and a substrate of elastin, and determining the amount of elastin activity, wherein a potentiation of elastase activity indicates inhibition of antileukoprotease activity and an inhibition of elastase activity indicates potentiation of antileukoprotease activity.  
     
     
         24 . The method of  claim 22  wherein measuring the amount of antileukoprotease activity comprises contacting antileukoprotease with cathepsin G and a substrate of cathepsin G, and determining the amount of elastin activity, wherein a potentiation of cathepsin G activity indicates inhibition of antileukoprotease activity and an inhibition of cathepsin G activity indicates potentiation of antileukoprotease activity.