Methods and compositions for the treatment and prevention of parkinson's disease

Abstract

Disclosed are therapeutic treatment methods, compositions and devices for maintaining neural pathways in a mammal, including enhancing survival of neurons at risk of dying, inducing cellular repair of damaged neurons and neural pathways, and stimulating neurons to maintain their differentiated phenotype. In one embodiment, the invention provides means for stimulating CAM expression in neurons. The invention also provides means for evaluating the status of nerve tissue, including means for detecting and monitoring neuropathies in a mammal. The methods, devices and compositions include a morphogen or morphogen-stimulating agent provided to the mammal in a therapeutically effective concentration.

What is claimed is:  
     
         1 . A method of treating Parkinson's disease, comprising administering a morphogen comprising a dimeric protein having an amino acid sequence selected from the group consisting of a sequence: 
 (a) having at least 70% homology with the C-terninal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2;    (b) having greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1;    (c) defined by Generic Sequence 7, SEQ ID NO: 4;    (d) defined by Generic Sequence 8, SEQ ID NO: 5;    (e) defined by Generic Sequence 9, SEQ ID NO: 6;    (f) defined by Generic Sequence 10, SEQ ID NO: 7, and    (g) defined by OPX, SEQ ID NO: 3,    wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.    
     
     
         2 . A method of restoring neural cell function in a mammal afflicted with Parkinson's disease, comprising administering a morphogen comprising a dimeric protein having an amino acid sequence selected from the group consisting of a sequence: 
 (a) having at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2;    (b) having greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1;    (c) defined by Generic Sequence 7, SEQ ID NO: 4;    (d) defined by Generic Sequence 8, SEQ ID NO: 5;    (e) defined by Generic Sequence 9, SEQ ID NO: 6;    (f) defined by Generic Sequence 10, SEQ ID NO: 7, and    (g) defined by OPX, SEQ ID NO: 3,    wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.    
     
     
         3 . A method of preserving neural cell function in a mammal afflicted with or at risk of Parkinson's disease, comprising administering a morphogen comprising a dimeric protein having an amino acid sequence selected from the group consisting of a sequence: 
 (a) having at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2;    (b) having greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1;    (c) defined by Generic Sequence 7, SEQ ID NO: 4;    (d) defined by Generic Sequence 8, SEQ ID NO: 5;    (e) defined by Generic Sequence 9, SEQ ID NO: 6;    (f) defined by Generic Sequence 10, SEQ ID NO: 7, and    (g) defined by OPX, SEQ ID NO: 3,    wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.    
     
     
         4 . A method of restoring the integrity of the nigrostriatal pathway in a mammal afflicted with Parkinson's disease, comprising administering a morphogen comprising a dimeric protein having an amino acid sequence selected from the group consisting of a sequence: 
 (a) having at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2;    (b) having greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1;    (c) defined by Generic Sequence 7, SEQ ID NO: 4;    (d) defined by Generic Sequence 8, SEQ ID NO: 5;    (e) defined by Generic Sequence 9, SEQ ID NO: 6;    (f) defined by Generic Sequence 10, SEQ ID NO: 7, and    (g) defined by OPX, SEQ ID NO: 3,    wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.    
     
     
         5 . A method of maintaining the integrity of the nigrostriatal pathway in a mammal afflicted with or at risk of Parkinson's disease, comprising administering a morphogen comprising a dimeric protein having an amino acid sequence selected from the group consisting of a sequence: 
 (a) having at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2;    (b) having greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1;    (c) defined by Generic Sequence 7, SEQ ID NO: 4;    (d) defined by Generic Sequence 8, SEQ ID NO: 5;    (e) defined by Generic Sequence 9, SEQ ID NO: 6;    (f) defined by Generic Sequence 10, SEQ ID NO: 7, and    (g) defined by OPX, SEQ ID NO: 3,    wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.    
     
     
         6 . A method of preventing degeneration of the nigrostriatal pathway in a mammal afflicted with or at risk of Parkinson's disease, comprising administering a morphogen comprising a dimeric protein having an amino acid sequence selected from the group consisting of a sequence: 
 (a) having at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2;    (b) having greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1;    (c) defined by Generic Sequence 7, SEQ ID NO: 4;    (d) defined by Generic Sequence 8, SEQ ID NO: 5;    (e) defined by Generic Sequence 9, SEQ ID NO: 6;    (f) defined by Generic Sequence 10, SEQ ID NO: 7, and    (g) defined by OPX, SEQ ID NO: 3,    wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.    
     
     
         7 . A method of treating Parkinson's disease, comprising administering a morphogen selected from the group consisting of human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, and BMP6, wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.  
     
     
         8 . A method of restoring neural cell function in a mammal afflicted with Parkinson's disease, comprising administering a morphogen selected from the group consisting of human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, and BMP6, wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.  
     
     
         9 . A method of preserving neural cell function in a mammal afflicted with or at risk of Parkinson's disease, comprising administering a morphogen selected from the group consisting of human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, and BMP6, wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.  
     
     
         10 . A method of restoring the integrity of the nigrostriatal pathway in a mammal afflicted with Parkinson's disease, comprising administering a morphogen selected from the group consisting of human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, and BMP6, wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.  
     
     
         11 . A method of maintaining the integrity of the nigrostriatal pathway in a mammal afflicted with or at risk of Parkinson's disease, comprising administering a morphogen selected from the group consisting of human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, and BMP6, wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.  
     
     
         12 . A method of preventing degeneration of the nigrostriatal pathway in a mammal afflicted with or at risk of Parkinson's disease, comprising administering a morphogen selected from the group consisting of human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vg1, Vgr-1, BMP3, BMP5, and BMP6, wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro.  
     
     
         13 . The method of  claim 1 ,  2 ,  3 ,  4 ,  5 ,  6 ,  7 ,  8 ,  9 ,  10 ,  11  or  12 , wherein said morphogen is complexed with at least one pro-domain polypeptide selected from the group consisting of the pro-domains of OP-1, OP-2, 60A, GDF-1, BMP-2A, BMP-2B, DPP, Vg1, Vgr-1, BMP-3, BMP-5, and BMP-6.  
     
     
         14 . The method of  claim 13 , wherein said morphogen is complexed with a pair of said pro-domain polypeptides.