Resumen
[0001] The invention relates to a SOCS1-derived peptide for use in chronic complications relating to diabetes, especially ocular, renal, nervous and vascular complications, and to compositions containing said peptide and isolated polynucleotides encoding for said peptide. The invention also relates to the topical use of said SOCS1-derived peptide in the treatment and/or prevention of neurodegenerative diseases of the retina, especially in the first stages of diabetic retinopathy and retina-related diseases wherein neurodegeneration plays an essential role. [0002] Peptide dérivé de SOCS1 pour son utilisation dans les complications chroniques du diabète, en particulier les complications oculaires, rénales, nerveuses et vasculaires, ainsi que compositions contenant ledit peptide et polynucléotides isolés codant pour ce peptide. La présente invention concerne en outre le peptide dérivé de SOCS1 pour son utilisation topique dans le traitement et/ou la prévention des affections neurodégénératives de la rétine, en particulier dans les premiers stades de la rétionopathie diabétique et d'autres affections de la rétine dans lesquelles la neurodégénérescence joue un rôle déterminant.
Reivindicaciones
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 any one of claims 1 or 2, 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 any one of claims 3 and 4, 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 any one of claims 1 to 3, 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 any one of claims 2 to 6, 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 any one of claims 1 to 6, consisting of the sequence SEQ ID NO 2 bound to a cell permeability region. 9. A polypeptide for use according to any one of claims 1 to 7, 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 any one of claims 1 to 10, where the tyrosine (Y) amino acid is phosphorylated. 12. A composition comprising a therapeutically effective amount of a polypeptide as defined in any one of claims 1 to 11, 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 any one of claims 12 and 13, 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.