Method for the prophylaxis and/or treatment of proliferative and/or inflammatory skin disorders

Abstract

The present invention relates generally to a method for the prophylaxis and/or treatment of skin disorders, and in particular proliferative and/or inflammatory skin disorders, and to genetic molecules useful for same. The present invention is particularly directed to genetic molecules capable of modulating growth factor interaction with its receptor on epidermal keratinocytes to inhibit, reduce or otherwise decrease stimulation of this layer of cells. The present invention contemplates, in a most preferred embodiment, a method for the prophylaxis and/or treatment of psoriasis.

1 . A method for ameliorating the effects of a proliferative and/or inflammatory skin disorder in a mammal, said method comprising contacting the proliferating and/or inflamed skin or skin capable of proliferation and/or inflammation with an effective amount of a nucleic acid molecule or chemical analogue thereof capable of inhibiting or otherwise reducing growth factor mediated cell proliferation and/or inflammation.  
     
     
         2 . A method according to  claim 1  wherein cell proliferation and/or inflammation is mediated by at least one of insulin-like growth factor I (IGF-I ), keratinocyte growth factor (KGF), transforming growth factor-α (TGFα), tumour necrosis factor-α (TNFα), interleukin (IL)-1 (IL-1), IL-4, IL-6, IL-8 and/or basic fibroblast growth factor (bFGF).  
     
     
         3 . A method according to  claim 2  wherein cell proliferation and/or inflammation is mediated by IGF-I.  
     
     
         4 . A method according to  claim 1  wherein the nucleic acid molecule inhibits or otherwise reduces IGF-I mediated cell proliferation and/or inflammation.  
     
     
         5 . A method according to  claim 1  wherein the proliferative or inflammatory skin disorder is psoriasis, ichthyosis, pityriasis, rubra, pilaris, serborrhoea, keloids, keratosis, neoplasias, scleroderma, warts, benign growths or cancers of the skin.  
     
     
         6 . A method according to  claim 5  wherein the skin condition is psoriasis.  
     
     
         7 . A method according to  claim 1  or  4  or  6  wherein the mammal is a human.  
     
     
         8 . A method according to  claim 1  or  4  or  6  wherein the nucleic acid molecule is capable of inhibiting, reducing or otherwise interfering with IGF-I-interaction with its receptor.  
     
     
         9 . A method according to  claim 8  wherein the nucleic acid molecule is an antisense molecule capable of reducing expression of a gene encoding IGF-I, IGF-I-receptor or an IGF binding protein (IGFBP).  
     
     
         10 . A method according to  claim 9  wherein the nucleic acid molecule is an antisense molecule capable of reducing expression of a gene encoding IGFBP-2, -3, -4, -5 or -6.  
     
     
         11 . A method according to  claim 10  wherein the nucleic acid molecule is an antisense molecule capable of reducing expression of a gene encoding IGFBP-2 or IGFBP-3.  
     
     
         12 . A method according to  claim 11  wherein the antisense molecule is at least about 15 nucleotides in length and is capable of interacting with at least one sequence selected from the list set forth in Example 6 or Example 7.  
     
     
         13 . A method according to  claim 11  wherein the antisense molecule comprises the nucleotide sequence:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   5′-ATCTCTCCGCTTCCTTTC-3′. 
                   [SEQ ID NO:10] 
                     
                 
                     
                     
                 
             
                
                
                
               
            
           
         
       
     
     
         14 . A nucleic acid molecule comprising at least about 10 nucleotides capable of hybridising to or forming a heteroduplex or otherwise interacting with an RNA molecule directed from a gene corresponding to a genomic form of SEQ ID NO: 1 and/or SEQ ID NO: 2 and which thereby reduces or inhibits translation of said RNA molecule.  
     
     
         15 . A nucleic acid molecule according to  claim 14  wherein said molecule comprises at least about 15 nucleotides.  
     
     
         16 . A nucleic acid molecule according to  claim 15  wherein said molecule is capable of interacting with at least one nucleotide sequence selected from the list set forth in Example 6 and Example 7.  
     
     
         17 . A nucleic acid molecule according to  claim 15  or  16  comprising the nucleotide sequence:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   5′-ATCTCTCCGCTTCCTTTC-3′. 
                   [SEQ ID NO:10] 
                     
                 
                     
                     
                 
             
                
                
                
               
            
           
         
       
     
     
         18 . A method of ameliorating the effects of psoriasis, said method comprising contacting proliferating skin or skin capable of proliferation with an effective amount of one or more nucleic acid molecules or chemical analogues thereof capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation wherein said one or more molecules comprises a polynucleotide capable of interacting with mRNA directed from an IGF-I gene, an IGF-I receptor gene or a gene encoding an IGFBP.  
     
     
         19 . A method according to  claim 18  wherein the IGFBP is IGFBP-2 or IGFBP-3.  
     
     
         20 . A method according to  claim 18  or  19  wherein the mammal is a human.  
     
     
         21 . A method according to  claim 20  wherein the nucleic acid molecule is capable of interacting with a nucleotide sequence selected from the list set forth in Example 6 or Example 7.  
     
     
         22 . A method according to  claim 18  wherein the nucleic acid molecule comprises the nucleotide sequence:  
       
         
           
                 
                 
                 
                 
               
                     
                     
                 
                     
                   5′-ATCTCTCCGCTTCCTTTC-3′. 
                   [SEQ ID NO:10] 
                     
                 
                     
                     
                 
             
                
                
                
               
            
           
         
       
     
     
         23 . A pharmaceutical composition for topical administration said composition comprising a nucleic acid molecule capable of inhibiting or otherwise reducing IGF-I mediated cell proliferation said composition further comprising one or more pharmaceutically acceptable carriers and/or diluents.  
     
     
         24 . A pharmaceutical composition according to  claim 23  wherein the nucleic acid molecule is an antisense molecule to a gene encoding IGF-I, IGF-I-receptor or an IGFBP.  
     
     
         25 . A pharmaceutical composition according to  claim 24  wherein the nucleic acid molecule is capable of targeting a gene encoding IGFBP-2 and/or IGFBP-3.  
     
     
         26 . A pharmaceutical composition according to  claim 24  capable of interacting with at least one nucleotide sequence set forth in Example 6 or Example 7.  
     
     
         27 . Use of a nucleic acid molecule in the manufacture of a medicament for the treatment of a proliferative and/or inflammatory skin disorder mediated by IGF-I.  
     
     
         28 . Use according to  claim 27  wherein the skin disorder is psoriasis.  
     
     
         29 . A ribozyme comprising a hybridising region and a catalytic region wherein the hybridising region is capable of hybridising to at least part of a target mRNA sequence transcribed from a genomic gene corresponding to SEQ ID NO: 1or SEQ ID NO: 2 wherein said catalytic domain is capable of cleaving said target mRNA sequence to reduce or inhibit IGF-I mediated cell proliferation or inflammation.