Methods and compositions for the treatment of axonal and neuronal degeneration

Abstract

The present invention generally relates to methods and compositions for preventing or treating axonal and/or neuronal degeneration in a subject by administering a composition comprising a peptide that comprises the amino acid sequence Arginine-Glycine-Aspartate (RGD).

1 - 35 . (canceled) 
     
     
         36 . A composition for treatment of conditions involving axonal and/or neuronal degeneration, comprising a peptide wherein the peptide is from about three to about fifty amino acids in length and comprises the amino acid sequence Arginine-Glycine-Aspartate (RGD). 
     
     
         37 . The composition of  claim 36 , wherein the peptide is from about three to about thirty amino acids long. 
     
     
         38 . The composition of  claim 36 , wherein the peptide is from about three to about fifteen amino acids long. 
     
     
         39 . The composition of  claim 36 , wherein the peptide is from about four to about eight amino acids in length. 
     
     
         40 . The composition of  claim 36 , wherein the RGD sequence is capable of binding to beta-1-integrin protein. 
     
     
         41 . The composition of  claim 36 , wherein the peptide is cyclic. 
     
     
         42 . The composition of  claim 36 , wherein the peptide comprises an amino acid sequence selected from the group consisting of (a) RGDYK (SEQ ID NO:1), GRGDS (SEQ ID NO:2), GRGDSP (SEQ ID NO:3), FRGDLG (SEQ ID NO:4), RRGDQT (SEQ ID NO:5), KRGDNF (SEQ ID NO:6), PRGDLT (SEQ ID NO:7), FRGDLP (SEQ ID NO:8), FRGDSP (SEQ ID NO:9), LRGDNPQ (SEQ ID NO:10), EKRGDRE (SEQ ID NO:11), GFRGDGQT (SEQ ID NO:12), WRGDGR (SEQ ID NO:13), ARGDV (SEQ ID NO:14), IRGDSP (SEQ ID NO:15), CRGDNG (SEQ ID NO:16) and YRGDTP (SEQ ID NO:17), (b) a conservatively modified variant of any of the foregoing amino acid sequences, and (c) an amino acid sequence that is at least about 70% identical to any of the foregoing amino acid sequences. 
     
     
         43 . The composition of  claim 36 , wherein the peptide comprises an amino acid sequence selected from the group consisting of cyclo-RGDYK (SEQ ID NO:1), GRGDS (SEQ ID NO:2), FRGDLG (SEQ ID NO:4), FRGDLP (SEQ ID NO:8), RRGDQT (SEQ ID NO:5), KRGDNF (SEQ ID NO:6), cyclo-IRGDSP (SEQ ID NO:15), cylco-FRGDSP (SEQ ID NO:9), cyclo-FRGDLP (SEQ ID NO:8) and cyclo-GRGDSP (SEQ ID NO:3). 
     
     
         44 . The composition of  claim 36 , wherein the peptide is subjected to a modification selected from the group consisting of is pegylation, cyclization, N-terminal acetylation, C-terminal amidation, phosphorylation of amino acids, and peptide biotinylation. 
     
     
         45 . The composition of  claim 36 , wherein the peptide comprises a fluorescent label. 
     
     
         46 . The composition of  claim 36 , wherein the peptide comprises one or more modified amino acids. 
     
     
         47 . The composition of  claim 36 , wherein the one or more modified amino acids are selected from the group consisting of D-amino-acids, L-beta-homo amino acids, D-beta-homo amino acids, N-methylated amino acids, and combinations thereof.