Treatment of aberrant fibroblast proliferation

Abstract

Provided is a method of preventing, treating or delaying progression of a disease involving aberrant fibroblast proliferation. The method involves using a compound that reduces the level of tyrosine phosphatase activity effected by the protein EYA1A in the parenchymal organ, a nucleic acid ligase IV inhibitor, or an antisense oligonucleotide against the p53-binding protein 1 (53BP1).

What is claimed is: 
     
         1 . A method of preventing, treating or delaying progression of a disease involving aberrant fibroblast proliferation in a parenchymal organ,
 wherein the method comprises administering at least one of a compound that reduces the level of tyrosine phosphatase activity effected by the protein EYA1A in said parenchymal organ, and/or   wherein the method comprises administering at least one of a compound that reduces the level of the protein EYA1A, a compound that effects the removal of exon 10 during splicing of a transcript of the Eya1 gene, or an inhibitor of the phosphotyrosine phosphatase activity of EYA1A.   
     
     
         2 . The method of  claim 1 , comprising administering at least one compound of:
 (a) an antisense oligonucleotide against at least one of a portion of at least 11 consecutive bases within the sequence of SEQ ID NO: 34, a complement of the portion within the sequence of SEQ ID NO: 34, an antisense oligonucleotide against at least one of a portion of at least 11 consecutive bases within the sequence of SEQ ID NO: 35, a complement of the portion within the sequence of SEQ ID NO: 35, an antisense oligonucleotide against at least one of a portion of at least 11 consecutive bases within the sequence of SEQ ID NO: 36, and a complement of the portion of the sequence of SEQ ID NO: 36;   (b) an inhibitor of the phosphotyrosine phosphatase activity of EYA1A selected from benzbromarone, a polyoxomolybdate phosphate complex, hexapotassium hexatriaconta-μ-oxooctadecaoxobis [μ9-[phosphato(3-)-κO:κO:κO:κO′:κO′:κO″:κO″:κO′″:κO′″]]octadeca-molybdate(6-), a salt having a cation of the formula   
       
         
           
           
               
               
           
         
         
           wherein R 1  and R 2  are independently selected C 1 -C 6  alkyl, R 3  is methyl or H, R 4 , R 5  and R 6  are independently selected from H, methyl and ethyl, and 
           a compound of the formula 
         
       
       
         
           
           
               
               
           
         
         
           wherein R 7  is one of H, OH, C 1 -C 6  alkoxy air phenoxy, R 8  and R 9  are independently selected from H and methyl, and R 10  is one of H, methyl, ethyl or (1-methyl-4-nitropyrazol-5-yl); or 
         
         (c) a nucleic acid molecule comprising an endonuclease 9 encoding sequence, a TET domain, and a sequence encoding an sgRNA specific for a portion of the sequence of one of SEQ ID NO: 6, 13, 21 or 22, each of the endonuclease 9 encoding sequence and the TET domain being operably linked to a promoter, wherein the promoters are independently selected.