Scientists at .NeuroRestore, Switzerland, report in Science that they have developed a gene therapy that was proven in mice to stimulate nerve regrowth across spinal cord injuries and guide nerves to reconnect to their natural targets to restore mobility
When the spinal cords of mice and humans are partially damaged, the initial paralysis is followed by the extensive, spontaneous recovery of motor function. However, after a complete spinal cord injury, this natural repair of the spinal cord doesn’t occur and there is no recovery. Meaningful recovery after severe injuries requires strategies that promote the regeneration of nerve fibers, but the requisite conditions for these strategies to successfully restore motor function have remained elusive.
In a new study in mice, a team of researchers from UCLA, the Swiss Federal Institute of Technology, and Harvard University have uncovered a crucial component for restoring functional activity after spinal cord injury. The neuroscientists have shown that re-growing specific neurons back to their natural target regions led to recovery, while random regrowth was not effective.
In a 2018 study published in Nature, the team identified a treatment approach that triggers axons — the tiny fibers that link nerve cells and enable them to communicate — to regrow after spinal cord injury in rodents. But even as that approach successfully led to the regeneration of axons across severe spinal cord lesions, achieving functional recovery remained a significant challenge.
For the new study, published in Science, the team aimed to determine whether directing the regeneration of axons from specific neuronal subpopulations to their natural target regions could lead to meaningful functional restoration after spinal cord injury in mice. They first used advanced genetic analysis to identify nerve cell groups that enable walking improvement after a partial spinal cord injury.
The researchers then found that merely regenerating axons from these nerve cells across the spinal cord lesion without specific guidance had no impact on functional recovery. However, when the strategy was refined to include using chemical signals to attract and guide the regeneration of these axons to their natural target region in the lumbar spinal cord, significant improvements in walking ability were observed in a mouse model of complete spinal cord injury.
This study provides crucial insights into the intricacies of axon regeneration and requirements for functional recovery after spinal cord injuries. It highlights the necessity of not only regenerating axons across lesions but also of actively guiding them to reach their natural target regions to achieve meaningful neurological restoration.
The researchers expect that their gene therapy will act synergistically with their other procedures involving electrical stimulation of the spinal cord. They believe a complete solution for treating spinal cord injury will require both approaches – gene therapy to regrow relevant nerve fibers, and spinal stimulation to maximize the ability of both these fibers and the spinal cord below the injury to produce movement.
While many obstacles must still be overcome before this gene therapy can be applied in humans, the scientists have taken the first steps towards developing the technology necessary to achieve this feat in the years to come.
The authors say understanding that re-establishing the projections of specific neuronal subpopulations to their natural target regions holds significant promise for the development of therapies aimed at restoring neurological functions in larger animals and humans. However, the researchers also acknowledge the complexity of promoting regeneration over longer distances in non-rodents, necessitating strategies with intricate spatial and temporal features. Still, they conclude that applying the principles laid out in their work will unlock the framework to achieve meaningful repair of the injured spinal cord and may expedite repair after other forms of central nervous system injury and disease.
News Source: Eurekalert
