In a world first, Australian researchers have discovered a mechanism for greatly enhancing regrowth of spinal cord nerves after they are damaged, restoring the ability to walk in mice within weeks of a spinal cord injury.
The University of Melbourne research team, led by Dr Ann Turnley at the Centre for Neuroscience and Professor Mary Galea at the School of Physiotherapy, found that removal of a molecule called EphA4 resulted in significant regrowth of the spinal nerves following injury.
Mice without EphA4 regained 100% of their initial stride length within three weeks of the injury and by one month had regained ankle and toe movement. Their ability to bear weight on the affected limbs, to walk and climb also improved and continued to do so for at least three months after the injury.
Anatomical analysis revealed that a large percentage of the spinal cord nerves had managed to grow across the damaged area of the spinal cord.
Dr Turnley says “when a person injures their spinal cord the effects are often devastating and there is usually little chance that they will regain much movement. There is an enormous amount of research being done around the world to enhance recovery of people with spinal injuries.
“In the past it was believed that adult nerves lacked the ability to regrow but work over the last few years has shown that not to be true and we are now beginning to understand the mechanisms behind regrowth and how to enhance it. Our recent findings are a major step forward in this regard.”
Dr Turnley says that EphA4 has been known for some time to be involved in guiding nerves during development but their role in the adult was unknown.
“The body enhances production of EphA4 following spinal cord injury and we thought it therefore could prove pivotal in determining the outcome of injury in the adult central nervous system.
“The surprising result we found was that EphA4 plays a vital role in activating cells called astrocytes which are in turn responsible for forming scarring in the damaged spinal cord, leading to inhibition of nerve regrowth. Mice without EphA4 have very little scarring in the spinal cord and so the nerves can regrow.”
Findings of the study, which will be published in The Journal of Neuroscience on November 10, are the work of PhD student Ms Yona Goldshmit, at the University of Melbourne’s Centre for Neuroscience and School of Physiotherapy, in collaboration with Professor Perry Bartlett, Director of the Queensland Brain Institute at the University of Queensland and formerly at the Walter and Eliza Hall Institute of Medical Research.
Professor Galea says “this finding provides an exciting possibility for overcoming spinal cord injuries and promoting nerve growth. Increased EphA4 expression has already been observed in primates following spinal cord injury and most likely plays a similar role in humans.
“There is now a real prospect of effectively promoting the regrowth of damaged spinal cord nerves after injury in humans by developing drugs that can block the EphA4 molecule and stop the scar from forming in the first place.”