Repair of the corticospinal tract

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After spinal cord injury patients lose sensation and are paralysed because the nerve fibres connecting the brain with the body are cut in the spinal cord. To restore full function these damaged fibres must be made to regenerate. Effective regeneration in the spinal cord has not been possible, but recent advances in Cambridge have made it possible to restore sensory regeneration in the spinal cord. Regeneration of motor fibres is more difficult, because unlike sensory fibres, the motor fibres mature to exclude many of the molecules needed for regeneration. The plan for this application is to bring together the method that made sensory regeneration possible with four candidate methods to enable growth-related molecules to be transported into the motor nerve fibres. The molecules that enable nerve fibre growth are integrins, which are transported into sensory fibres but not motor fibres. Research on transport mechanisms has developed four methods the enable integrins to be transported into mature nerve fibres and to restore their ability to regenerate in a tissue culture model.The plan for the application is to develop viral vectors suitable for use in rats for each of these treatments. The treatments will then be tested in combination to find out the most powerful treatment for inducing regeneration. Some of the successful combinations will then be tested in quick proof of principle experiments in rats with partial spinal cord damage to identify the best method for restoring regeneration. Finally the best two treatments will be tested in a full experiment in which regeneration and behavioural recovery will be measured.