Nogo, caspr, f3 nb-3 useful in the treatment of injury and disease to the central nervous system

Abstract

The application provides materials and methods for promoting myelination of neuronal axons in the CNS. These derive from the findings firstly that the molecules Nogo and Caspr interact with one another during establishment and maintenance of the axoglial junction, and secondly that the molecules F3 and NB-3 are capable of promoting oligodendrocyte maturation via interaction with Notch. The materials and methods provided may be used in the treatment of CNS damage, in particular the treatment of spinal cord injury, multiple sclerosis, epilepsy and stroke.

1 . A composition comprising Nogo and Caspr, or mimetics thereof, or a substance capable of promoting interaction between Nogo and Caspr, in combination with a carrier.  
   
   
       2 . A composition according to  claim 1  wherein the composition comprises a complex between Nogo and Caspr, or a mimetic of said complex.  
   
   
       3 . A composition according to  claim 1  comprising Nogo-66.  
   
   
       4 . A composition according to  claim 1  comprising Caspr1.  
   
   
       5 . A composition according to  claim 1  wherein the substance capable of promoting interaction between Nogo and Caspr is an antibody.  
   
   
       6 . A composition according to  claim 5  wherein the antibody is capable of binding to both Nogo and Caspr.  
   
   
       7 . A composition according to  claim 1 , which is a pharmaceutical composition.  
   
   
       8 . A pharmaceutical composition according to  claim 7  which is formulated for injection in vivo.  
   
   
       9 . A pharmaceutical composition according to  claim 8  which is formulated for direct injection into the CNS.  
   
   
       10 .- 15 . (canceled)  
   
   
       16 . A method of stimulating myelination of a neural axon, comprising contacting a neuron or an oligodendroglial cell with a composition according to  claim 1 .  
   
   
       17 . A method of treating a subject having disease of, or injury to, the central nervous system, comprising administering to the subject a pharmaceutical composition according to  claim 7 .  
   
   
       18 . A method according to  claim 17  wherein the subject has SCI, MS, epilepsy or stroke.  
   
   
       19 . A method of screening for a substance capable of modulating interaction between Nogo and Caspr, the method comprising contacting Nogo, Caspr and a candidate substance, and determining the interaction between Nogo and Caspr.  
   
   
       20 . A method according to  claim 19  further comprising contacting Nogo and Caspr in the absence of said candidate substance under otherwise analogous conditions, and determining the interaction between Nogo and Caspr.  
   
   
       21 . A method according to  claim 19  comprising contacting a complex between Nogo and Caspr with the candidate substance.  
   
   
       22 . A method according to  claim 19  wherein one of Nogo and Caspr is present in or on a cell.  
   
   
       23 . A method according to  claim 22  wherein said one of Nogo and Caspr is expressed from a vector introduced into said cell.  
   
   
       24 . A method according to  claim 19  wherein one of Nogo and Caspr is immobilised on a solid support.  
   
   
       25 . A method of manufacturing a pharmaceutical formulation comprising, having identified a substance capable of modulating interaction between Nogo and Caspr by a method according to  claim 19 , the further step of formulating said substance with a pharmaceutically acceptable carrier.  
   
   
       26 . A method according to  claim 25  comprising the further step of optimising said substance for administration in vivo.  
   
   
       27 .- 62 . (canceled)