Par1 modulation to alter myelination

Abstract

Materials and methods for modulating protease activated receptor 1 (PAR1) activity to alter myelination are provided.

What is claimed is: 
     
         1 . A method for modulating myelination in a mammal, comprising;
 (a) identifying the mammal as being in need of increased myelination; and   (b) administering to the mammal an agent that reduces the activity of protease activated receptor 1 (PAR1).   
     
     
         2 . The method of  claim 1 , wherein the agent is an siRNA, an antisense nucleic acid molecule, an antibody against PAR1, or a small molecule inhibitor of PAR1. 
     
     
         3 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         4 . The method of  claim 3 , wherein the human is a preterm infant. 
     
     
         5 . The method of  claim 3 , wherein the human is an adult. 
     
     
         6 . The method of  claim 1 , wherein the mammal is identified as having a central nervous system (CNS) demyelinating disease, CNS neuroinflammatory disease, or stroke. 
     
     
         7 . The method of  claim 1 , wherein the mammal is identified as having a CNS injury. 
     
     
         8 . A method for treating a CNS demyelinating disorder in a mammal, comprising administering to the mammal a composition comprising an agent that reduces the activity of PAR1, wherein the composition is administered in an amount effective to reduce or prevent demyelination, or to enhance remyelination. 
     
     
         9 . The method of  claim 8 , wherein the agent is an siRNA, an antisense nucleic acid molecule, an antibody against PAR1, or a small molecule inhibitor of PAR1. 
     
     
         10 . The method of  claim 8 , wherein the mammal is a human. 
     
     
         11 . The method of  claim 10 , wherein the human is a preterm infant. 
     
     
         12 . The method of  claim 10 , wherein the human is an adult. 
     
     
         13 . The method of  claim 8 , wherein the CNS demyelinating disorder is a CNS demyelinating disease, CNS neuroinflammatory disease, or stroke. 
     
     
         14 . The method of  claim 8 , wherein the CNS demyelinating disorder is a CNS injury. 
     
     
         15 . A method for modulating myelination in a subject, comprising delivering to the subject a plurality of modified stem cells that have reduced PAR expression as compared to corresponding wild type stem cells. 
     
     
         16 . The method of  claim 15 , wherein the subject is a human. 
     
     
         17 . The method of  claim 16 , wherein the human is an adult with a demyelinating disorder. 
     
     
         18 . The method of  claim 16 , wherein the human is a preterm infant. 
     
     
         19 . The method of  claim 15 , wherein the stem cells are neural stem cells. 
     
     
         20 . The method of  claim 19 , wherein the neural stem cells comprise a mutation in the PAR1 gene.