Chimeric protein
A chimeric protein is disclosed for promoting repair and regeneration of neurons damaged by disease or physical injury wherein the chimeric protein is a combination of a first polypeptide possessing matrix modification activity and a second polypeptide possessing regenerating activity for neural cells.
1 . A chimeric protein comprising:
1) a first polypeptide possessing matrix modification activity; and
2) a second polypeptide possessing regenerating activity for neural cells,
said first and second polypeptides not occurring together in nature and being joined together in said chimeric protein.
2 . The chimeric protein of claim 1 wherein the first polypeptide is selected from the group consisting of chondroitinases, hyaluronidases, and matrix metalloproteinases.
3 . The chimeric protein of claim 2 wherein the chondroitinase is selected from the group consisting of chondroitinase ABC exolyase, chondroitinase ABC endolyase, Chondroitinase AC, and Chondroitinase B.
4 . The chimeric protein of claim 2 wherein the matrix metalloproteinase is selected from the group consisting of MMP-9, MMP-2, and pepsin.
5 . The chimeric protein of claim 1 wherein the second polypeptide is selected from the group consisting of neural cell adhesion molecules (N-CAM), L1, N-CAM, myelin-associated glycoproteins, laminins, fibronectins, cadherins, Tenascins, FNA-D, M1 antibodies, netrins, BSP-2 (mouse N-CAM), D-2, 224-1A6-A1, NILE, Nr-CAM, TAG-1 (axonin-1), Ng-CAM, F3/F11, integrins, J1, Fasciclin III, MAG molecules and neurotrophic factors.
6 . The chimeric protein of claim 5 wherein the second polypeptide is L1.
7 . The chimeric protein of claim 5 wherein the cadherin is selected from the group consisting of N-cadherin, E-cadherin, P-cadherin, L-CAM, B-cadherin, and T-cadherin.
8 . The chimeric protein of claim 5 wherein the tenascin is Tenascin-C.
9 . The chimeric protein of claim 5 wherein the neurotrophic factor is selected from the group consisting of NGF, BDNF, NT-3, IGF, EGF, VEGF, FGF, PDGF, TGF □ and □ and GG{tilde over (F)}
10 . The chimeric protein of claim 1 wherein the first polypeptide is joined to the second polypeptide by a peptide linkage.
11 . The chimeric protein of claim 9 wherein the peptide linkage is an Fc portion of an immunoglobulin.
12 . A method for enhancing nervous system repair and regeneration by administering to damaged cells of the nervous system a chimeric protein comprising:
1) a first polypeptide possessing matrix modification activity; and
2) a second polypeptide possessing regenerating activity for neural cells,
said first and second polypeptides not occurring together in nature and being joined together in said chimeric protein.
13 . The chimeric protein of claim 12 wherein the chondroitinase is selected from the group consisting of chondroitinase ABC I, chondroitinase ABC II, Chondroitinase AC, and Chondroitinase B.
14 . The method of claim 12 wherein the chondroitinase is chondroitinase ABC I.
15 . The method of claim 12 wherein the matrix metalloproteinase is selected from the group consisting of MMP-9, MMP-2, and pepsin.
16 . The method of claim 15 wherein the second polypeptide is L1.
17 . The method of claim 15 wherein the cadherin is selected from the group consisting of N-cadherin, E-cadherin, P-cadherin, L-CAM, B-cadherin, and T-cadherin.
18 . The method of claim 15 wherein the tenascin is Tenascin-C.
19 . The chimeric protein of claim 5 wherein the neurotrophic factor is selected from the group consisting of NGF, BDNF, NT-3, IGF, EGF, VEGF, FGF, PDGF, TGF □ and □ and GG{tilde over (F)}
20 . The method of claim 11 wherein the first polypeptide is joined to the second polypeptide by a peptide linkage.
21 . The method of claim 19 wherein the peptide linkage is an Fc portion of an immunoglobulin.
22 . A pharmaceutical composition comprising a chimeric protein in combination with a pharmaceutically acceptable carrier, wherein the chimeric protein comprises:
1) a first polypeptide possessing matrix modification activity; and
2) a second polypeptide possessing regenerating activity for neural cells,
said first and second polypeptides being joined by a peptide linkage in said chimeric protein.
23 . The method of claim 12 wherein the second polypeptide is selected from the group consisting of neural cell adhesion molecules (N-CAM), L1, N-CAM, myelin-associated glycoproteins, laminins, fibronectins, cadherins, Tenascins, FnA-D, M1 antibodies, netrins, BSP-2 (mouse N-CAM), D-2, 224-1A6-A1, NILE, Nr-CAM, TAG-1 (axonin-1), Ng-CAM, F3/F11, integrins, J1, Fasciclin III, MAG molecules and neurotrophic factors.
24 . The method of claim 12 wherein the first polypeptide is selected from the group consisting of chondroitinases, hyaluronidases, and matrix metalloprotienases.