Socs1-derived peptide for use in chronic complications of diabetes

Abstract

The present invention relates to a SOCS1-derived peptide for use in chronic complications of diabetes, particularly ocular, renal, nerve and vascular complications, as well as compositions containing same and isolated polynucleotides encoding same. The present invention also relates to the SOCS1-derived peptide for topical use in the treatment and/or prevention of neurodegenerative diseases of the retina, particularly in the early stages of diabetic retinopathy and other diseases of the retina in which neurodegeneration plays an essential role.

What is claimed is: 
     
         1 . An isolated polypeptide comprising:
 a) the sequence of SEQ ID NO 2; or   b) a variant of the sequence of a) which is at least 85% identical to SEQ ID NO 2, based on the identity of all the amino acids of said sequence;   for use in the prevention or treatment of chronic complications of diabetes and/or neurodegenerative diseases of the retina, where chronic complications of diabetes are selected from the group consisting of diabetic retinopathy, macular edema, diabetic nephropathy, diabetic angiopathies, diabetic microangiopathies, diabetic macroangiopathies, diabetic atherosclerosis, diabetic foot and peripheral artery disease, and where neurodegenerative diseases of the retina are selected from the group consisting of diabetic retinopathy, glaucoma and retinitis pigmentosa.   
     
     
         2 . The polypeptide for use according to  claim 1 , where the chronic complication of diabetes and/or the neurodegenerative disease of the retina is diabetic retinopathy. 
     
     
         3 . The polypeptide for use according to  claim 1 , where the sequence SEQ ID NO 2 or the at least 85% identical variant thereof is bound to a cell permeability region. 
     
     
         4 . The polypeptide for use according to  claim 3 , wherein the cell permeability region is lysine-palmitate. 
     
     
         5 . The polypeptide for use according to  claim 3 , wherein the cell permeability region is bound at the N-terminal end of the peptide sequence (residue D, aspartic acid). 
     
     
         6 . The polypeptide for use according to  claim 1 , consisting essentially of
 a) the sequence of SEQ ID NO 2; or   b) a variant of the sequence of a) which is at least 85% identical to SEQ ID NO 2, based on the identity of all the amino acids of said sequence.   
     
     
         7 . The polypeptide for use according to  claim 2 , essentially consisting of
 a) the murine SOCS1 protein (UniProt: 035716);   b) the human SOCS1 protein (UniProt: 015524); or   c) a variant of the sequence of a) or b) which is at least 85% homologous to the amino acid sequence of the murine SOCS1 protein or to the amino acid sequence of the human SOCS1 protein.   
     
     
         8 . The polypeptide for use according to  claim 1 , consisting of the sequence SEQ ID NO 2 bound to a cell permeability region. 
     
     
         9 . A polypeptide for use according to  claim 1 , wherein at least one amino acid of the sequence thereof is phosphorylated. 
     
     
         10 . The polypeptide for use according to  claim 9 , where at least one of the phosphorylated amino acids is a tyrosine (Y) amino acid. 
     
     
         11 . The polypeptide for use according to  claim 1 , where the tyrosine (Y) amino acid is phosphorylated. 
     
     
         12 . A composition comprising a therapeutically effective amount of a polypeptide as defined in  claim 1 , and at least one pharmaceutically acceptable vehicle or excipient, for use in the prevention or treatment of chronic complications of diabetes or in the prevention or treatment of a neurodegenerative disease of the retina, where chronic complications of diabetes are selected from the group consisting of diabetic retinopathy, macular edema, diabetic nephropathy, diabetic angiopathies, diabetic microangiopathies, diabetic macroangiopathies, diabetic atherosclerosis, diabetic foot and peripheral artery disease, and where neurodegenerative diseases of the retina are selected from the group consisting of diabetic retinopathy, glaucoma and retinitis pigmentosa. 
     
     
         13 . The composition according to  claim 12 , suitable for use orally, gastroenterically, parenterally, rectally, by respiratory route or topically, particularly ophthalmically. 
     
     
         14 . The composition according to  claim 12 , for use in the prevention or treatment of diabetic retinopathy. 
     
     
         15 . The composition according to  claim 14 , where the vehicle is a pharmaceutically acceptable ophthalmic vehicle. 
     
     
         16 . An isolated polynucleotide encoding
 a) the amino acid sequence SEQ ID NO 2; or   b) a variant of the sequence of a) which is at least 85% identical to the sequence SEQ ID NO 2, based on the identity of all the nucleotides of said sequence;   for use in the prevention or treatment of chronic complications of diabetes and/or neurodegenerative diseases of the retina, where chronic complications of diabetes are selected from the group consisting of diabetic retinopathy, macular edema, diabetic nephropathy, diabetic angiopathies, diabetic microangiopathies, diabetic macroangiopathies, diabetic atherosclerosis, diabetic foot and peripheral artery disease, and where neurodegenerative diseases of the retina are selected from the group consisting of diabetic retinopathy, glaucoma and retinitis pigmentosa.   
     
     
         17 . An isolated polynucleotide encoding
 a) the amino acid sequence SEQ ID NO 2 bound to a lysine group; or   b) a variant of the sequence of a) which is at least 85% identical to the sequence SEQ ID NO 2, bound to a lysine group, based on the identity of all the nucleotides of said sequence; for use in the prevention or treatment of chronic complications of diabetes and/or neurodegenerative diseases of the retina, where chronic complications of diabetes are selected from the group consisting of diabetic retinopathy, macular edema, diabetic nephropathy, diabetic angiopathies, diabetic microangiopathies, diabetic macroangiopathies, diabetic atherosclerosis, diabetic foot and peripheral artery disease, and where neurodegenerative diseases of the retina are selected from the group consisting of diabetic retinopathy, glaucoma and retinitis pigmentosa.