Scientists from the Swiss company NeuroRestore reported in the journal Science that they have developed a gene therapy that has been proven in mice to stimulate nerve regeneration at spinal cord injuries and guide nerves to reconnect to their natural targets, thereby restoring mobility.
Whole spinal cord visualization of lower thoracic spinal cord regenerative processes projecting to the walking executive center. Image source: EPFL/.Neurorestore
When parts of the spinal cord are damaged in mice and humans, initial paralysis is followed by widespread, spontaneous recovery of motor function. However, after a complete spinal cord injury, this natural repair of the spinal cord does not occur, and recovery is impossible. Effective recovery after severe injury requires strategies to promote nerve fiber regeneration, but the conditions necessary for these strategies to successfully restore motor function remain elusive.
"Five years ago, we demonstrated that nerve fibers could regenerate in anatomically intact spinal cord injuries," said Mark Anderson, senior author of the study. "But we also realized that this was not enough to restore motor function because the new fibers failed to connect to the correct location on the other side of the lesion." Anderson is director of CNS Regeneration at NeuroRestore and a scientist at the Wyss Center for Biological and Neural Engineering.
Whole-cord visualization of lower thoracic spinal cord regeneration projecting to the walking executive center. Image source: EPFL/.Neurorestore
Working with colleagues at the University of California, Los Angeles (UCLA) and Harvard Medical School, the scientists used advanced equipment at the EPFL Campus Biotechnology Facility in Geneva to conduct in-depth analyzes and determine which types of neurons are involved in the natural repair of the spinal cord after partial spinal cord injury. Jordan Squair, the study's first author, said: "Our observations using single-cell nuclear RNA sequencing not only revealed the specific axons that must regenerate, but also revealed that these axons must reconnect with their natural targets to restore motor function." The research team's findings were published in the September 22, 2023 issue of Science.
Their findings provide a basis for designing multi-pronged gene therapies. The scientists activated the growth program of identified neurons in mice to regenerate nerve fibers; upregulated specific proteins to support neuronal growth through the core of the lesion; and administered guidance molecules to attract regenerating nerve fibers to natural targets beneath the lesion. "We were inspired by nature when we designed a treatment strategy that replicates some of the spinal cord repair mechanisms that occur spontaneously after injury," Squair said.
Whole spinal cord visualization of lower thoracic spinal cord regenerative processes projecting to the walking executive center. Image source: EPFL/.Neurorestore
Mice with anatomically complete spinal cord injuries regained the ability to walk and exhibited a gait similar to that of mice that returned to natural walking after partial injury. This observation reveals an unknown condition for regenerative therapy to successfully restore motor function after neurotrauma. "We hope that our gene therapy will work in synergy with our other procedures involving electrical stimulation of the spinal cord," said Grégoire Courtine and Jocelyne Bloch, senior authors of the study and principals of NeuroRestore. "We believe that a complete solution for treating spinal cord injury requires two approaches - gene therapy to regrow the relevant nerve fibers, and spinal cord stimulation to maximize the ability of those fibers and the spinal cord to generate movement at the site of the injury."
While many hurdles must be overcome before this type of gene therapy can be used in humans, scientists have taken the first steps and are developing the necessary technology to make this feat a reality in the coming years.