Methods and compositions for the treatment of motor neuron injury and neuropathy

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.

1 - 9 . (Canceled)  
     
     
         10 . A method of preserving motor function in a mammal with symptoms of or at risk of amyotrophic lateral sclerosis, comprising administering to said mammal a morphogen, wherein the morphogen: 
 (1) comprises a dimeric protein having an amino acid sequence with: 
 (a) 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; or  
 (g) defined by OPX, SEQ ID NO: 3; and  
   (2) stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro;    whereby motor function is preserved in said mammal.    
     
     
         11 . (Canceled)  
     
     
         12 . A method of preserving motor function in a mammal with symptoms of or at risk of a spinal cord injury, comprising administering to said mammal a morphogen, wherein the morphogen: 
 (1) comprises a dimeric protein having an amino acid sequence with: 
 (a) at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2;  
 (b) 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; or  
 (g) defined by OPX, SEQ ID NO: 3; and  
   (2) stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro;    whereby motor function is preserved in said mammal.    
     
     
         13 - 18 . (Canceled)  
     
     
         19 . A method of preserving motor function in a mammal with symptoms of or at risk of amyotrophic lateral sclerosis, comprising administering to said mammal a morphogen selected from: human OP-1, mouse OP-1, human OP-2, mouse OP-2,60A, GDF-1, BMP2A, BMP2B, DPP, Vgl, Vgr-1, BMP3, BMP5, or BMP6, wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro whereby motor function is preserved in said mammal.  
     
     
         20 . (Canceled)  
     
     
         21 . A method of preserving motor function in a mammal with symptoms of or at risk of a spinal cord injury, comprising administering a morphogen selected from: human OP-1, mouse OP-1, human OP-2, mouse OP-2, 60A, GDF-1, BMP2A, BMP2B, DPP, Vgl, Vgr-1, BMP3, BMP5, or BMP6, wherein said morphogen stimulates production of an N-CAM or L1 isoform by an NG108-15 cell in vitro whereby motor function is preserved in said mammal.  
     
     
         22 - 23 . (Canceled)  
     
     
         24 . The method of  claim 10 , wherein the morphogen comprises a dimeric protein having an amino acid sequence with at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2.  
     
     
         25 . The method of  claim 10 , wherein the morphogen comprises a dimeric protein having an amino acid sequence with greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1.  
     
     
         26 . The method of  claim 12 , wherein the morphogen comprises a dimeric protein having an amino acid sequence with at least 70% homology with the C-terminal seven-cysteine skeleton of human OP-1, residues 330-431 of SEQ ID NO: 2.  
     
     
         27 . The method of  claim 12 , wherein the morphogen comprises a dimeric protein having an amino acid sequence with greater than 60% amino acid sequence identity with said C-terminal seven-cysteine skeleton of human OP-1.