Targeting neuronal maturation to promote axon regeneration after spinal cord injury

Spinal cord injury leads to permanent and severe paralysis and loss of sensation. The principal reason for this is that nerve cells connecting the brain with the rest of the body lose the capacity to regenerate their processes (axons) as they mature during development. Despite decades of progress, no regenerative therapy for the injured spinal cord is available today, making a regenerative treatment for spinal cord injury a major unmet need of the British Columbia healthcare system. In this project, we will focus on the fundamental processes through which maturation suppresses axon regeneration. We have discovered a molecular switch that is turned off in mature neurons and that we hypothesize is critical for nerve cells to regrow axons. We will study how this molecular switch is turned off during maturation, the processes that it controls to enable growth and test whether re-activating it in mature neurons can promote regeneration and functional improvements following spinal cord injury. Collectively, this work will provide critical insight into why mature nerve cells fail to regenerate. We anticipate that this work will be a major steppingstone towards the development of a treatment that regenerates the injured human spinal cord.