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Spinal cord repair: releasing the neuron-intrinsic brake on axon regeneration
Problem: Spinal cord injury (SCI) leads to permanent disability and is a significant clinical problem with 130.000 new cases/year worldwide. Following SCI long axon tracts fail to regenerate. This is the primary reason for the sustained loss of bodily functions. Aim: AxonRepair aims to develop a strategy to promote long-distance axon regeneration in the injured spinal cord by reprogramming neurons into a regenerative state and by overcoming the axon transport block that is a barrier to axon regeneration. In AxonRepair we brought together world-class experts on transcriptional control of axon regeneration, axon transport and therapeutic gene delivery. Workplan: Work package (WP) 1 aims to reprogram neurons into a regenerative state by testing the effect of gene therapeutic combinatorial delivery of key transcription factors identified in our collective?s discovery pipeline. WP 2 aims to restore axonal transport of growth-related axonal receptors. WP 3 provides novel mechanistic insight into how interventions at the transcriptional and the axon transport level work and whether these interventions act synergistically on axon regeneration. Exploitation of results: At completion of the project we expect to have developed a method to release the brake on axon regeneration. The participation of the gene therapy company UniQure ensures that newly generated know-how will be exploited rapidly by entering in a co-development agreement and/or intellectual property strategy.
Gene targeting in the brain, Molecular modelling techniques, "omics" approaches, axon regeneration, gene therapy, transcription factor, integrin, axon-initial segment