When the spinal cord, in both mice and people, is partially damaged, extensive and spontaneous recovery of motor function is possible after the initial paralysis. However, after a complete spinal cord injury, this natural repair does not occur and therefore there is no recovery.
The key is to regenerate the nerve fibers, but until now it had not been achieved. The study is published in ‘Science‘.
“Five years ago we demonstrated that nerve fibers can regenerate in anatomically complete spinal cord injuries,” he says. Mark Anderson, lead author of the study and director of Central Nervous System Regeneration at NeuroRestore. But, he adds, “we also realized that this was not enough to restore motor function, since the new fibers failed to connect to the correct places on the other side of the injury.”
We knew, comments Jordan Squair, first author of the study, that “specific neurons have to be regenerated in a certain place, but “How do you know what type of neuron and where?”
Working in collaboration with the team at UCLA and Harvard, the scientists used state-of-the-art equipment to perform in-depth analysis and identify what type of neuron is involved in the natural repair of the spinal cord after partial spinal cord injury. “Our observations not only revealed the specific axons that must be regenerated, but also revealed that these axons must reconnect to their natural targets to restore motor function,” explains Squair.
This expert points out that were inspired by nature to design a therapeutic strategy that replicates the repair mechanisms of the spinal cord that occur spontaneously after partial injuries. That is, “we analyze using state-of-the-art technology how the neurons in animals react to achieve spontaneous recovery of the ability to walk.” “And we found that type of neuron that, if activated, allowed the animal to walk again.”
Neuronal regeneration Whole-spinal cord visualization of regenerative projections from the lower thoracic spinal cord that project to gait execution centers. EPFL/.Neurorestore
“We used a cocktail of growth factors through gene therapy to guide axons through the spinal cord to the right place. And when that happens, the ability to walk is regenerated,” adds Squair.
The team designed a multifaceted gene therapy. First, they activated growth programs in neurons identified in mice to regenerate their nerve fibers, upregulated specific proteins to support the growth of neurons through the lesion core, and administered guide molecules to attract regenerating nerve fibers to their natural targets below the injury.
Mice with anatomically complete spinal cord injuries treated with this gene therapy regained the ability to walk, exhibiting gait patterns that resembled those quantified in mice that resumed walking naturally after partial injuries.
This observation revealed a previously unknown condition for regenerative therapies to be successful in restoring motor function after neurotrauma. “We hope that our gene therapy will act synergistically with other procedures that involve electrical stimulation of the spinal cord,” he says. Grégoire Courtinelead author of the study and director of NeuroRestore.
Courtine’s team and Jocelyne Bloch has made great advances in the treatment of people with spinal cord injuries. In 2022, his team designed a system that reestablishes communication between the brain and the spinal cord through a wireless digital implant that allowed people with paraplegia to walk again naturally with crutches, even when the implant was turned off, by recovering functions. neurological problems that he had lost since his accident.
However, Courtine, although he recognizes that much progress has been made in recovering the ability to walk in people with spinal cord injury through neurostimulation, “we believe that a complete solution for the treatment of spinal cord injury will require both approaches“Gene therapy to regrow relevant nerve fibers and spinal cord stimulation to maximize the ability of both these fibers and the spinal cord beneath the injury to produce movement.”
While many obstacles still need to be overcome before this gene therapy can be applied to humans, scientists have taken the first steps toward developing the technology needed to achieve this feat in the coming years.
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