Neuroprotective peptides

Abstract

The invention relates to the use of an isolated peptide of 10 to 32 amino acid residues in length for the treatment of neural injury, wherein the isolated peptide comprises at least 10 to 22 arginine residues. The peptide may be a poly-arg sequence or an arginine-rich peptide.

1 - 30 . (canceled) 
     
     
         31 . An isolated peptide for the treatment or prevention of neural injury, said isolated peptide comprising 10 to 32 amino acid residues in length, wherein the isolated peptide includes at least 10 to 22 arginine residues. 
     
     
         32 . The peptide as claimed in  claim 31 , wherein the isolated peptide has an arginine content of at least 30%. 
     
     
         33 . The peptide as claimed in  claim 32 , wherein the isolated peptide has an arginine residue content of at least 90%. 
     
     
         34 . The peptide as claimed in  claim 31 , wherein the isolated peptide is a poly-arginine peptide comprising 10 to 18 arginine residues. 
     
     
         35 . The peptide as claimed in  claim 31 , wherein the isolated peptide comprises any one or more of the peptides selected from the group consisting of SEQ. ID. NOS. 7, 8, 9, 10, 11, 12, 13, 16, 22, 30, 31, 32, 33, 34, 35, 36, 37, and functional fragments and analogues thereof having neuroprotective activity. 
     
     
         36 . The peptide as claimed in  claim 31 , wherein the isolated peptide includes at least one poly-arginine segment comprising at least 4 contiguous arginine residues. 
     
     
         37 . The peptide as claimed in  claim 31 , wherein the isolated peptide comprises a mix of protamine derivatives. 
     
     
         38 . The peptide as claimed in  claim 37 , wherein the mix of protamine derivatives comprises protamine sulphate. 
     
     
         39 . The peptide as claimed in  claim 31 , wherein the isolated peptide treats or prevents neural injury by one or more mechanisms selected from the group consisting of promoting the survival of neurons, inhibiting neuronal cell death, affecting the endocytic processes of the cell; affecting the function of cell surface receptors to result in reduced cellular calcium influx; interacting with and/or stabilises the outer mitochondrial membrane to preserve mitochondrial function; and inhibiting, downregulating, or affecting the calcium-dependent pro-protein convertase enzyme furin. 
     
     
         40 . The peptide of  claim 32 , wherein the isolated peptide is included within, or fused to, one or more polypeptides. 
     
     
         41 . The peptide of  claim 40 , wherein the isolated peptide is fused to a second peptide with at least one linker sequence. 
     
     
         42 . The peptide of  claim 32 , wherein the isolated peptide exhibits neuroprotective activity at IC50 levels of less than 10 μM. 
     
     
         43 . An isolated polynucleotide sequence encoding a peptide for the treatment or prevention of neural injury, said polynucleotide sequence comprising:
 a codon sequence coding for a 10 to 32 amino acid peptide having at least 10 to 22 arginine residues,   a complementary sequence that is complementary to the codon sequence,   a hybridization sequence that hybridizes under stringent conditions with the codon sequence, and   a homology sequence having at least 60% homology with the codon sequence,   wherein the isolated polynucleotide sequence is a non-naturally occurring polynucleotide, a man-made artificial construct, cDNA, or a vector including the isolated nucleic acids.   
     
     
         44 . The isolated polynucleotide sequence as claimed in  claim 43 , wherein the isolated polynucleotide sequence is incorporated into a pharmaceutical composition for the treatment or prevention of neural injury. 
     
     
         45 . The isolated polynucleotide sequence as claimed in  claim 44 , wherein the pharmaceutical composition is selected from the group consisting of ion exchangers, alumina, aluminium stearate, lecithin, serum proteins, buffers, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat. 
     
     
         46 . A pharmaceutical composition for the treatment or prevention of a neural injury, for promoting survival of neurons and/or for inhibiting cell death, the pharmaceutical composition or medicament including a peptide of 10 to 32 amino acid residues, wherein the peptide comprises at least 10 to 22 arginine residues. 
     
     
         47 . The pharmaceutical composition of  claim 45 , for use in the treatment or prevention of ischemia, perinatal hypoxia-ischemia, Alzheimer's disease, Huntington's Disease, Multiple Sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stroke, peripheral neuropathy, spinal cord injury, pain or epilepsy. 
     
     
         48 . The pharmaceutical composition of  claim 45 , wherein a dosage for administration is from 0.001 mg/kg to 50 mg/kg. 
     
     
         49 . The pharmaceutical composition of  claim 48 , wherein the dosage is administered orally. 
     
     
         50 . The pharmaceutical composition of  claim 46 , wherein the pharmaceutical composition further includes carriers selected from the group consisting of ion exchangers, alumina, aluminium stearate, lecithin, serum proteins, buffers, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethylcellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol and wool fat.