Modulation of ciliogenesis

Abstract

The disclosure is based on the finding that compounds capable of binding to (or interacting with) chromatin binding/remodelling complexes (for example Polycomb group PRC1 and Trithorax group MLL) and/or modulation of the same can be used to modulate (for example switch on/off) ciliogenesis as may occur, for example, in the human pulmonary bronchial epithelium. Provided are compounds, compositions, methods and medicaments which may be used to treat and/or prevent diseases and/or conditions associated with aberrant or defective ciliogenesis.

1 . A method of treating and/or preventing diseases and/or conditions associated with aberrant or defective ciliogenesis, said method comprising administering a subject in need thereof a therapeutically effective amount of a compound which binds, associates or interacts with PRC1 and/or TrxG-MLL. 
     
     
         2 . The method of  claim 1 , wherein the compound modulates or mimics the expression, function and/or activity of the gene designated regenerative gene for respiratory cells 1 (R2R1). 
     
     
         3 . The method of  claim 1 , wherein the compound binds to or associates with, R2R1 binding sites within the PRC1 and/or TrxG-MLL complexes. 
     
     
         4 . The method of  claim 1 , wherein the compound interferes with, prevents or inhibits binding between native or wild type R2R1 and PRC1TrxG-MLL and/or a component or subunit of either. 
     
     
         5 . The method of  claim 1 , wherein the compound binds to or associates with the Ring Finger Protein 2 (RNF2) subunit of PRC1. 
     
     
         6 . The method of  claim 1 , wherein the compound binds to or associates with the DPY-30 and/or ASH2L subunit proteins of TrxG-MII. 
     
     
         7 . The method of  claim 1 , wherein the compound is selected from the group consisting of a nucleic acid; an antisense oligonucleotide; a carbohydrate; a protein/peptide; a small molecule; and an antibody or an antigen or target binding fragment thereof 
     
     
         8 . The method of  claim 1 , wherein the compound is encoded by SEQ ID NO: 1, 2, 3 or 4 or a fragment thereof. 
     
     
         9 . The method of  claim 1  wherein the compound comprises a sequence corresponding to SEQ ID NO: 5 or 6 or a fragment thereof. 
     
     
         10 . The method of  claim 1 , wherein the compound is an antisense oligonucleotide which reduces, inhibits and/or ablates the expression, function and/or activity of the R2R1 gene. 
     
     
         11 . The method of  claim 1 , wherein the compound is an antibody capable of binding R2R1 or an R2R1 binding site within the PRC1 and/or TrxG-MLL complexes. 
     
     
         12 . (canceled) 
     
     
         13 . The method of  claim 1 , wherein the disease and/or condition associated with aberrant or defective ciliogenesis is a ciliopathy. 
     
     
         14 . The method of  claim 1 , wherein the disease and/or condition associated with aberrant or defective ciliogenesis chronic obstructive pulmonary disorder (COPD). 
     
     
         15 .- 21 . (canceled) 
     
     
         22 . A method of treating or preventing diseases and/or conditions associated with aberrant or defective ciliogenesis, said method comprising administering a subject in need thereof a therapeutically effective amount of a compound which modulates the expression of the R2R1 gene and/or the activity, function and/or expression of the R2R1 protein/peptide in cells. 
     
     
         23 . The method of  claim 22 , wherein the disease and/or condition associated with aberrant or defective ciliogenesis is a ciliopathy. 
     
     
         24 . The method of  claim 22 , wherein the disease and/or condition associated with aberrant or defective ciliogenesis is chronic obstructive pulmonary disorder (COPD).