Methods and compositions for nerve regeneration

Abstract

Methods and compositions for modulating growth of a neuron with a Wnt, a Wnt-like substance, and/or a chemical compound affecting a Wnt signaling pathway are disclosed. Also disclosed are methods for identifying a substance that modulates growth of a neuron by obtaining a candidate substance and contacting the candidate substance with the neuron are disclosed and methods for modulating growth of a neuron in a subject using a Wnt, a Wnt-like substance, and/or a chemical compound affecting a Wnt signaling pathway. The Wnt, Wnt-like substance, and/or chemical compounds affecting a Wnt signaling pathway can be delivered to the subject using gene therapy techniques. Also disclosed are pharmaceutical compositions for modulating growth of a neuron in a mammal that include a Wnt or a Wnt-like substance. Methods and compositions for inhibiting growth of a neuron are also disclosed.

1 . A method for modulating the directional growth of a mammalian neuron comprising contacting the neuron with an inhibitor of frizzled. 
     
     
         2 . The method of  claim 1 , wherein the frizzled inhibitor comprises a frizzled antibody. 
     
     
         3 . The method of  claim 2 , wherein the frizzled antibody inhibits a frizzled selected from the group consisting of frizzled3, frizzled8, and frizzled9. 
     
     
         4 . The method of  claim 1 , wherein the neuron is contacted with the inhibitor in a spinal cord. 
     
     
         5 . The method of  claim 4 , wherein the inhibitor is provided as a concentration gradient. 
     
     
         6 . The method of  claim 5 , wherein the concentration gradient is provided as a decreasing anterior-posterior concentration gradient along the spinal cord. 
     
     
         7 . The method of  claim 4 , wherein the directional growth of the neuron occurs along the anterior-posterior axis of the spinal cord. 
     
     
         8 . The method of  claim 4 , wherein the directional growth of the neuron is along the spinothalamic pathway. 
     
     
         9 . The method of  claim 4 , wherein the spinal cord has been damaged. 
     
     
         10 . The method of  claim 1 , wherein the neuron is a commissural neuron. 
     
     
         11 . The method of  claim 10 , wherein the commissural neuron is contacted with the inhibitor post-midline crossing. 
     
     
         12 . The method of  claim 1 , wherein the frizzled inhibitor comprises a sFRP. 
     
     
         13 . The method of  claim 12 , wherein the sFRP is selected from sFRP1, sFRP2 and sFRP3. 
     
     
         14 . The method of  claim 1 , wherein the neuron is further contacted with a neuronal growth inhibitor. 
     
     
         15 . The method of  claim 1 , wherein the neuron is further contacted with a substance that blocks activity of a neuronal growth inhibitor. 
     
     
         16 . The method of  claim 1 , wherein the neuron is a motor neuron or a sensory neuron. 
     
     
         17 . The method of  claim 1 , wherein the neuron is a damaged neuron. 
     
     
         18 . The method of  claim 17 , wherein the directional growth of the neuron facilitates regeneration of the neuron. 
     
     
         19 . The method of  claim 1 , wherein the inhibitor repels neuronal growth. 
     
     
         20 . The method of  claim 1 , wherein the inhibitor is provided as a pharmaceutical composition.