Promoting axon renegeration in the adult cns through control of protein translation

Abstract

Disclosed are methods for promoting survival of, or axon regeneration in a lesioned mature central nervous system (CNS) by contacting the neuron with a therapeutically effective amount of an exogenous activator of protein translation. Detecting the resultant promotion of the survival of, or axon regeneration in the neuron may further be performed. The methods may be performed using an inhibitor of phosphatase and tensin homolog (PTEN). Pharmaceutical compositions and preloaded devices for use in the methods are also disclosed.

What is claimed is: 
     
         1 . A device for promoting survival of, or axon regeneration in a lesioned mature human neuron in vivo, wherein the lesion results from a traumatic spinal cord injury, comprising a reservoir loaded with a premeasured and contained amount of a pharmaceutical composition comprising a therapeutically effective amount of an inhibitor of phosphatase and tensin homolog (PTEN). 
     
     
         2 . The device of  claim 1 , which further comprises a nerve growth factor, trophic factor, or hormone that promotes neural cell survival, growth, and/or differentiation. 
     
     
         3 . The device of  claim 1  wherein the device further comprises brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), inosine, oncomodulin, NT-3, and combinations thereof. 
     
     
         4 . The device of  claim 1 , wherein the pharmaceutical composition is formulated for ocular administration. 
     
     
         5 . The device of  claim 1 , wherein the pharmaceutical composition is formulated for intravenous administration. 
     
     
         6 . The device of  claim 1 , wherein the pharmaceutical composition is formulated for intrathecal administration. 
     
     
         7 . The device of  claim 1 , which is implantable. 
     
     
         8 . A device for promoting survival of, or axon regeneration in a lesioned mature central nervous system (CNS) neuron in vivo determined to have axotomy-induced stress and/or pathology-induced down-regulation of protein translation, comprising a reservoir loaded with a premeasured and contained amount of a therapeutically effective amount of an activator of protein translation in the neuron, and specifically adapted for implementing contacting the neuron with the activator of protein translation, to thereby promote survival of, or axon regeneration in the neuron. 
     
     
         9 . The device of  claim 8 , wherein the activator of protein translation is an inhibitor of phosphatase and tensin homolog (PTEN), and wherein the lesion results from a spinal cord injury. 
     
     
         10 . A method for promoting survival of, or axon regeneration in a lesioned mature neuron in vivo, wherein the lesion results from a traumatic spinal cord injury, comprising contacting the lesioned neuron with a therapeutically effective amount of a PTEN inhibitor to thereby promote survival of, or axon regeneration in the neuron. 
     
     
         11 . The method of  claim 10 , further comprising detecting the resultant promotion of the survival of, and axon regeneration in the neuron. 
     
     
         12 . The method of  claim 11 , wherein the detecting step is by an indirect assay of axon regeneration. 
     
     
         13 . The method of  claim 11 , wherein the detecting step is by a direct assay of axon regeneration. 
     
     
         14 . The method of  claim 10 , wherein the inhibitor is administered locally at the neuron.