PROJECT: JTC2016: AxonRepair

Spinal cord repair: releasing the neuron-intrinsic brake on axon regeneration

Abstract

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.

Keywords

Gene targeting in the brain, Molecular modelling techniques, "omics" approaches, axon regeneration, gene therapy, transcription factor, integrin, axon-initial segment

Call topic

External Insults

Proposed runtime

2017 - 2021

Project team

Joost Verhaagen (Coordinator)
The Netherlands (NWO)
James Fawcett
United Kingdom (MRC)
Lawrence Moon
United Kingdom (MRC)
Frank Bradke
Germany (BMBF)
Alyson Fournier
Canada (FRQS)
Dasa Cizkova
Slovakia (SAS)