Neuritogenic peptides

Abstract

The present invention relates to peptide compounds that are capable of stimulating neuronal differentiation, neurite outgrowth and survival of neural cells, and enhancing synaptic plasticity, learning and memory, methods of treating diseases and conditions of nervous system by administration of compositions comprising said compounds. The compounds and compositions of the invention include peptide sequences that are derived from the sequence of human erythropoietin or proteins that are homologous of human erythropoietin.

1 . A method for treating a condition of the central or peripheral nervous system, said method comprising administering to a subject in need thereof an effective amount of a composition comprising (i) a peptide consisting of 6 to 20 consecutive amino acids of SEQ ID NO:3; or (ii) a peptide having a length of not more than 20 amino acids and including 6 to 20 consecutive amino acids of SEQ ID NO:3, wherein said peptide has more than 80% homology to SEQ ID NO:3; or (iii) a peptide having a length of not more than 20 amino acids and including a variant of a fragment of SEQ ID NO:3, said fragment having 6 to 20 consecutive amino acids of SEQ ID NO:3 and said variant having more than 80% homology to said fragment; wherein said peptide is capable of stimulating neurite outgrowth, and/or promoting survival of neural cells, and/or stimulating neural cell proliferation. 
     
     
         2 . The method of  claim 1 , wherein said condition of the central or peripheral nervous system is a neurodegenerative disease. 
     
     
         3 . The method of  claim 2 , wherein said neurodegenerative disease is Alzheimer's disease, Parkinson's disease or Huntington's disease. 
     
     
         4 . The method of  claim 1 , wherein said condition of the central or peripheral nervous system is cerebral ischemia. 
     
     
         5 . The method of  claim 1 , wherein said condition of the central or peripheral nervous system is postoperative nerve damage, traumatic nerve damage or traumatic brain injury. 
     
     
         6 . The method of  claim 1 , wherein said condition of the central or peripheral nervous system is selected from the group consisting of epilepsy, dementia, sclerosis, schizophrenia, impaired myelination of nerve fibers, nerve degeneration associated with diabetes mellitus, disorders affecting the circadian clock or neuromuscular transmission or mood disorders. 
     
     
         7 . The method of  claim 1 , wherein the subject is human. 
     
     
         8 . The method of  claim 1 , wherein the composition comprises a monomer of (i) a peptide consisting of 6 to 20 consecutive amino acids of SEQ ID NO:3, or (ii) a peptide having a length of not more than 20 amino acids, including 6 to 20 consecutive amino acids of SEQ ID NO:3, and having more than 80% homology to SEQ ID NO:3, or (iii) a peptide having a length of not more than 20 amino acids and including a variant of a fragment of SEQ ID NO:3, said fragment having 6 to 20 consecutive amino acids of SEQ ID NO:3 and said variant having more than 80% homology to said fragment. 
     
     
         9 . The method of  claim 1 , wherein the composition comprises two or more peptides, the peptides either (i) consisting of 6 to 20 consecutive amino acids of SEQ ID NO:3, or (ii) having a length of not more than 20 amino acids, including 6 to 20 amino acids of SEQ ID NO:3, and having more than 80% homology to SEQ ID NO:3, or (iii) having a length of not more than 20 amino acids and including a variant of a fragment of SEQ ID NO:3, said fragment having 6 to 20 consecutive amino acids of SEQ ID NO:3 and said variant having more than 80% homology to said fragment; wherein said two or more peptides are linked via one or more linker groups. 
     
     
         10 . The method of  claim 9 , wherein said linker group is selected from the group consisting of peptide bonds forming a polymer of the two or more polypeptides, dendrimeric polymers, Ligand Presenting Assembly (LPA)-type polymers, lysine dendrimers, bovine serum albumin (BSA), lipophilic dendrimers, micelle-like carriers, starburst carbon chain polymer conjugates, and ligand presenting assembly polymers based on derivatives of diethylaminomethane, with the proviso that the amino acid sequence of each copy of the peptide is not identical to the amino acid sequence of naturally occurring erythropoietin 
     
     
         11 . The method of  claim 9 , wherein the composition comprises a dimer or a tetramer of said peptides. 
     
     
         12 . The method of  claim 1 , wherein the composition comprises a peptide having a length of not more than 20 amino acids and including (i) a fragment of SEQ ID NO:3 having 10 to 15 consecutive amino acids of SEQ ID NO:3, or (ii) a variant of said fragment, said variant having more than 80% homology to said fragment. 
     
     
         13 . The method of  claim 1 , wherein the composition comprises a peptide having an amino acid sequence consisting of from 10 to 15 amino acids of SEQ ID NO:3. 
     
     
         14 . The method of  claim 1 , wherein the composition comprises a peptide consisting of the amino acid sequence of SEQ ID NO:3. 
     
     
         15 . The method of  claim 1 , wherein the arginine amino acid residue at position 12 of SEQ ID NO:3 is arginine or conservatively substituted with a histidine or a lysine amino acid residue in the corresponding position within said peptide.