Use of transforming growth factor - beta 1 (tgf-b1) inhibitor peptides for the treatment of corneal fibrosis and/or haze

Abstract

The invention refers to the use of transforming growth factor-beta 1 (TGF-β1) inhibitor peptides or polynucleotides encoding said peptides for the prevention and/or treatment of corneal fibrosis and/or corneal haze.

1 . A product selected from the group consisting of:
 a) a TGF-β1 inhibitor peptide, or a functionally equivalent derivative, variant, analog or fragment thereof,   b) a fusion protein comprising a peptide as defined in a),   c) a polynucleotide encoding a peptide as defined in a) or a fusion protein as defined in b),   d) a vector comprising a polynucleotide as defined in c),   e) a cell comprising a peptide as defined in a), a fusion protein as defined in b), a polynucleotide as defined in c) and/or a vector as defined in d), and   f) a combination of one or more of a), b), c), d), and/or e),   
       for use in the prevention and/or treatment of corneal fibrosis and/or corneal haze. 
     
     
         2 . Product according to  claim 1 , in the form of a composition comprising one or more of said products a) to e). 
     
     
         3 . Product according to  claim 1  or  2 , wherein said TGF-β1 inhibitor peptide is a peptide having at least 70% sequence identity to an amino acid sequence of any of the amino acid sequences shown under SEQ ID NO: 1-23. 
     
     
         4 . Product according to  claim 1  or  2 , wherein said TGF-β1 inhibitor peptide is a peptide selected from the group of peptides whose amino acid sequence is shown in SEQ ID NO: 1, or in SEQ ID NO: 2, or in SEQ ID NO: 3, or in SEQ ID NO: 4, or in SEQ ID NO: 5, or in SEQ ID NO: 6, or in SEQ ID NO: 7, or in SEQ ID NO: 8, or in SEQ ID NO: 9, or in SEQ ID NO: 10, or in SEQ ID NO: 11, or in SEQ ID NO: 12, or in SEQ ID NO: 13, or in SEQ ID NO: 14, or in SEQ ID NO: 15, or in SEQ ID NO: 16, or in SEQ ID NO: 17, or in SEQ ID NO: 18, or in SEQ ID NO: 19, or in SEQ ID NO: 20, or in SEQ ID NO: 21, or in SEQ ID NO: 22, or in SEQ ID NO: 23, or a functionally equivalent derivative, variant, analog, or fragment thereof, or a salt thereof. 
     
     
         5 . Product according to  claim 4 , wherein said fragment comprises 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 consecutive amino acid residues of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, or SEQ ID NO: 23, and maintains the capacity to inhibit TGF-β1. 
     
     
         6 . Product according to  claim 1  or  2 , wherein said TGF-β1 inhibitor peptide is a peptide selected from the group of peptides p144 (SEQ ID NO: 6), p17 (SEQ ID NO: 17) or a fragment comprising 9, 10, 11, 12, 13, or 14 consecutive amino acid residues of SEQ ID NO: 6 or SEQ ID NO: 17, or their pharmaceutically acceptable salts, wherein said fragment maintains the capacity to inhibit TGF-β1. 
     
     
         7 . Product according to  claim 1  or  2 , wherein said TGF-β1 inhibitor peptide is selected from the group of peptides consisting of p144 (SEQ ID NO: 6), p17 (SEQ ID NO: 17) and combinations thereof. 
     
     
         8 . Use of a product selected from the group consisting of
 a) a TGF-β1 inhibitor peptide, or a functionally equivalent derivative, variant, analog or fragment thereof,   b) a fusion protein comprising a peptide as defined in a),   c) a polynucleotide encoding a peptide as defined in a) or a fusion protein as defined in b),   d) a vector comprising a polynucleotide as defined in c),   e) a cell comprising a peptide as defined in a), a fusion protein as defined in b), a polynucleotide as defined in c) and/or a vector as defined in d), and   f) a combination of one or more of a), b), c), d), and/or e),   
       for use in the manufacture of a pharmaceutical composition for the prevention and/or treatment of corneal fibrosis and/or corneal haze. 
     
     
         9 . A method for the prevention and/or treatment of corneal fibrosis or corneal haze which comprises administering to a subject in need of treatment a therapeutically effective amount of a product selected from the group consisting of:
 a) a TGF-β1 inhibitor peptide, or a functionally equivalent derivative, variant, analog or fragment thereof,   b) a fusion protein comprising a peptide as defined in a),   c) a polynucleotide encoding a peptide as defined in a) or a fusion protein as defined in b),   d) a vector comprising a polynucleotide as defined in c),   e) a cell comprising a peptide as defined in a), a fusion protein as defined in b), a polynucleotide as defined in c) and/or a vector as defined in d), and   f) a combination of one or more of (a), (b), (c), (d), and/or (e).   
     
     
         10 . An ophthalmic pharmaceutical composition comprising a therapeutically effective amount of a product selected from the group consisting of:
 a) a TGF-β1 inhibitor peptide, or a functionally equivalent derivative, variant, analog or fragment thereof,   b) a fusion protein comprising a peptide as defined in a),   c) a polynucleotide encoding a peptide as defined in a) or a fusion protein as defined in b),   d) a vector comprising a polynucleotide as defined in c),   e) a cell comprising a peptide as defined in a), a fusion protein as defined in b), a polynucleotide as defined in c) and/or a vector as defined in d), and   f) a combination of one or more of (a), (b), (c), (d), and/or (e); and   
       a pharmaceutically acceptable vehicle for said compound(s) wherein said pharmaceutically acceptable vehicle is a vehicle suitable for ophthalmic administration.