Methods and kits for treating and diagnosing leiomyomas

Abstract

This invention provides methods of treating a subject suffering from a leiomyoma which comprise administering to the subject a therapeutically effective amount of an agent, or alternatively a plurality of agents, which inhibit specific metalloproteinases. This invention further provides diagnostic methods of determining whether a tumor in a subject is a leiomyoma. This invention further provides pharmaceutical compositions and kits for practicing the instant methods. Finally, this invention provides a method of determining whether an agent specifically inhibits certain metalloproteinases.

What is claimed is:  
     
         1 . A method of treating a subject suffering from a leiomyoma which comprises administering to the subject a therapeutically effective dose of an agent which specifically inhibits at least one metalloproteinase selected from the group consisting of stromelysin-2, stromelysin-3 and matrilysin.  
     
     
         2 . A pharmaceutical composition for treating a subject suffering from a leiomyoma which comprises an agent which specifically inhibits at least one metalloproteinase selected frog the group consisting of stromelysin-2, stromelysin-3 and matrilysin, and a pharmaceutically acceptable carrier.  
     
     
         3 . A method of treating a subject suffering from a leiomyoma which comprises administering to the subject a therapeutically effective dose of the pharmaceutical composition of  claim 2 .  
     
     
         4 . The method of  claim 1  or  3 , wherein the subject is a human.  
     
     
         5 . The method of  claim 1  or  3 , wherein the leiomyoma is a uterine leiomyoma.  
     
     
         6 . The method of  claim 1  or  3 , wherein the agent specifically inhibits stromelysin-2.  
     
     
         7 . The method of  claim 1  or  3 , wherein the agent specifically inhibits stromelysin-3.  
     
     
         8 . The method of  claim 1  or  3 , wherein the agent specifically inhibits matrilysin.  
     
     
         9 . The method of  claim 1  or  3 , wherein the agent specifically inhibits stromelysin-2, stromelysin-3 and matrilysin.  
     
     
         10 . A method of treating a subject suffering from a leiomyoma which comprises administering to the subject a therapeutically effective dose of a plurality of agents, each of which specifically inhibits at least one metalloproteinase selected from the group consisting of stromelysin-2, stromelysin-3 and matrilysin.  
     
     
         11 . A pharmaceutical composition for treating a subject suffering from a leiomyoma which comprises a plurality of agents, each of which specifically inhibits at least one metalloproteinase selected from the group consisting of stromelysin-2, stromelysin-3 and matrilysin, and a pharmaceutically acceptable carrier.  
     
     
         12 . A method of treating a subject suffering from a leiomyoma which comprises administering to the subject a therapeutically effective dose of the pharmaceutical composition of  claim 11 .  
     
     
         13 . The method of  claim 10  or  12 , wherein the subject is a human.  
     
     
         14 . The method of  claim 10  or  12 , wherein the leiomyoma is a uterine leiomyoma.  
     
     
         15 . The method of  claim 10  or  12 , wherein the agent specifically inhibits stromelysin-2.  
     
     
         16 . The method of  claim 10  or  12 , wherein the agent specifically inhibits stromelysin-3.  
     
     
         17 . The method of  claim 10  or  12 , wherein the agent specifically inhibits matrilysin.  
     
     
         18 . The method of  claim 10  or  12 , wherein the agent specifically inhibits stromelysin-2, stromelysin-3 and matrilysin.  
     
     
         19 . A method of determining whether a tumor in a subject is a leiomyoma, which comprises the steps of 
 (a) obtaining a sample of the tumor from the subject;    (b) determining the amount of at least one metalloproteinase present in the sample, the metalloproteinase being selected from the group consisting of stromelysin-2, stromelysin-3 and matrilysin; and    (c) comparing the amount of each metalloproteinase determined in step (b) to a known standard, thereby determining whether the tumor is a leiomyoma.    
     
     
         20 . A method of determining whether a tumor in a subject is a leiomyoma, which comprises the steps of 
 (a) obtaining a sample of the tumor prom the subject;    (b) determining the amount of at least one metalloproteinase-encoding mRNA present in the sample, the metalloproteinase being selected from the group consisting of stromelysin-2, stromelysin-3 and matrilysin; and    (c) comparing the amount of each metalloproteinase-encoding mRNA determined in step (b) to a known standard, thereby determining whether the tumor is a leiomyoma.    
     
     
         21 . The method of  claim 19  or  20 , wherein the subject is a human.  
     
     
         22 . The method of  claim 19  or  20 , wherein the leiomyoma is a uterine leiomyoma.  
     
     
         23 . The method of  claim 19  or  20 , wherein the metalloproteinase is stromelysin-3.  
     
     
         24 . The method of  claim 23 , wherein the metalloproteinase is stromelysin-2, stromelysin-3 and matrilysin.  
     
     
         25 . A kit for use in determining whether a tumor in a subject is a leiomyoma, which comprises 
 (a) an agent suitable for determining the amount of a metalloproteinase present in a tumor sample taken from the subject, the metalloproteinase being selected from the group consisting of stromelysin-2, stromelysin-3 and matrilysin; and    (b) a known standard with which the amount of each metalloproteinase determined in step (a) can be compared, so as to permit determining whether the tumor is a leiomyoma.    
     
     
         26 . The kit of  claim 25 , wherein the agent suitable for determining the amount of a metalloproteinase is an antibody.  
     
     
         27 . A kit for use in determining whether a tumor in a subject is a leiomyoma, which comprises 
 (a) an agent suitable for determining the amount of a metalloproteinase-encoding mRNA present in a tumor sample taken from the subject, the metalloproteinase being selected from the group consisting of stromelysin-2, stromelysin-3 and matrilysin; and    (b) a known standard with which the amount of each metalloproteinase-encoding mRNA determined in step (a) can be compared, so as to, permit determining whether the tumor is a leiomyoma.    
     
     
         28 . The kit of  claim 27 , wherein the agent suitable for determining the amount of a metalloproteinase-encoding mRNA is a detectable nucleic acid probe.  
     
     
         29 . A method of determining whether an agent specifically inhibits at least one metalloproteinase selected from the group consisting of stromelysin-2, stromelysin-3 and matrilysin, which comprises determining whether the agent 
 (a) slows the reaction rate of stromelysin-2, stromelysin-3 or matrilysin by a factor of at least 50, and    (b) does not slow the reaction rate of any metalloproteinase, other than stromelysin-2, stromelysin-3, matrilysin, and gelatinase a and b, by more than a factor of 25,    whereby an agent satisfying the criteria of parts (a) and (b) is one which specifically inhibits at least one metalloproteinase selected from the group consisting of stromelysin-2, stromelysin-3 and matrilysin.