Methods of promoting cns neuronal repair by inhibiting lrp-1

Abstract

This invention provides methods for promoting and/or restoring neurite outgrowth and neuronal regeneration by contacting an injured neuron with an inhibitor of low density lipoprotein receptor-related protein-1 (LRP-1).

1 .- 28 . (canceled) 
     
     
         29 . A method of enhancing nerve growth or neuronal regeneration, comprising contacting a neuron with an inhibitor of low density lipoprotein receptor-related protein-1 (LRP-1) expression in the presence of a myelin-associated inhibitory protein, wherein the inhibitor of LRP-1 is an inhibitory nucleic acid. 
     
     
         30 . The method of  claim 29 , wherein the neuron is a central nervous system neuron. 
     
     
         31 . The method of  claim 29 , wherein the neuron is in vitro. 
     
     
         32 . The method of  claim 29 , wherein the neuron is in vivo. 
     
     
         33 . The method of  claim 29 , wherein the myelin-associated inhibitory protein is selected from the group consisting of myelin associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), Nogo-A, Nogo-B, Nogo-C, ephrin-B3, Sema4D/CD100, repulsive guidance molecule b, and fragments thereof. 
     
     
         34 . The method of  claim 29 , wherein the inhibitory nucleic acid is delivered in a viral vector. 
     
     
         35 . The method of  claim 29 , wherein the inhibitory nucleic acid is selecting from the group consisting of an siRNA, an shRNA, an antisense RNA, or a ribozyme. 
     
     
         36 . The method of  claim 29 , wherein the inhibitor nucleic acid is an LRP-1 specific siRNA. 
     
     
         37 . The method of  claim 29 , wherein the inhibitory nucleic acid is an LRP-1 specific siRNA comprising the nucleotide sequence of SEQ ID NO: 9. 
     
     
         38 . A method of enhancing nerve growth or neuronal regeneration in a subject in need thereof, comprising administering to the subject an effective amount of an inhibitor of low density lipoprotein receptor-related protein-1 (LRP-1) expression, wherein the inhibitor of LRP-1 expression is an inhibitory nucleic acid, and wherein the subject is a human. 
     
     
         39 . The method of  claim 38 , wherein the subject has experienced an injury to the central nervous system. 
     
     
         40 . The method of  claim 38 , wherein the subject has experienced a spinal cord injury. 
     
     
         41 . The method of  claim 38 , wherein the subject has experienced a traumatic brain injury. 
     
     
         42 . The method of  claim 39 , wherein the inhibitor of LRP-1 expression is administered directly to the injury. 
     
     
         43 . The method of  claim 38 , wherein the inhibitory nucleic acid is delivered in a viral vector. 
     
     
         44 . The method of  claim 38 , wherein the inhibitory nucleic acid is selecting from the group consisting of an siRNA, an shRNA, an antisense RNA, or a ribozyme. 
     
     
         45 . The method of  claim 38 , wherein the inhibitor nucleic acid is an LRP-1 specific siRNA. 
     
     
         46 . The method of  claim 38 , wherein the inhibitory nucleic acid is an LRP-1 specific siRNA comprising the nucleotide sequence of SEQ ID NO: 9.