Nogo Receptor-Mediated Blockade of Axonal Growth

Abstract

Disclosed are NgR proteins and biologically active Nogo (ligand) protein fragments. Also disclosed are compositions and methods for modulating the expression or activity of the Nogo and NgR protein. Also disclosed are peptides which block Nogo-mediated inhibition of axonal extension. The compositions and methods of the invention are useful in the treatment of cranial or cerebral trauma, spinal cord injury, stroke or a demyelinating disease.

1 - 39 . (canceled) 
     
     
         40 . A method of inhibiting CNS myelin-mediated neurite outgrowth inhibition or promoting axonal regeneration comprising contacting a neuron with a Nogo receptor (NgR) antagonist selected from the group consisting of:
 (a) an isolated NgR polypeptide; and   (b) an antibody or antigen binding fragment thereof that binds an NgR polypeptide;   wherein said NgR antagonist inhibits CNS myelin-induced neurite outgrowth inhibition or promotes axonal regeneration.   
     
     
         41 . A method of promoting neurite outgrowth or axonal regeneration in a mammal comprising administering to a mammal in need thereof an effective amount of a Nogo receptor (NgR) antagonist, wherein said NgR antagonist is selected from the group consisting of:
 (a) an isolated NgR polypeptide; and   (b) an antibody or antigen binding fragment thereof that binds an NgR polypeptide;   wherein said NgR antagonist inhibits CNS myelin-induced neurite outgrowth inhibition or promotes axonal regeneration.   
     
     
         42 . A method of treating a central nervous system disease, disorder or injury in a mammal, comprising administering to a mammal in need thereof an effective amount of an NgR antagonist selected from the group consisting of:
 (a) an isolated NgR polypeptide; and   (b) an antibody or antigen binding fragment thereof that binds an NgR polypeptide;   wherein said NgR antagonist inhibits CNS myelin-induced neurite outgrowth inhibition or promotes axonal regeneration.   
     
     
         43 . The method of  claim 42 , wherein said central nervous system disease, disorder or injury is selected from the group consisting of cranial or cerebral trauma, spinal cord injury, stroke, multiple sclerosis, monophasic demyelination, encephalomyelitis, multifocal leukoencephalopathy, panencephalitis, Marchiafava-Bignami disease, pontine myelinolysis, adrenoleukodystrophy, Pelizaeus-Merzbacher disease, Spongy degeneration, Alexander's disease, Canavan's disease, metachromatic leukodystrophy, and Krabbe's disease.