Nature: New study identifies neurons that allow lumbar spinal epidural electrical stimulation to restore movement in paralyzed patients

In a multi-year research program coordinated by Grégoire Courtine, professor of neuroscience at the Ecole Polytechnique Fédérale de Lausanne in Switzerland, and Jocelyne Bloch and Jordan W.
Squair, neurosurgeons at the University Hospital de Lausanne, patients paralyzed by spinal cord injury were able to regain some motor function
after directed epidural stimulation of the lumbar spinal cord, which controls leg movement.
In a new study, Courtine, Bloch, Squair, and their research team not only demonstrated the effectiveness of this therapy in 9 patients, but also sustained improvements in motor function after the neurological rehabilitation process ended and electrical stimulation was turned off
.
This indicates that the nerve fibers used for walking have been reorganized
.
They believe that it is crucial to understand exactly how this neural fiber reconstruction occurs in order to develop more effective treatments and improve the lives
of as many patients as possible.
The results of the study were published online in the journal Nature on November 9, 2022, under the title "The neurons that restore walking after paralysis"
.
To gain this understanding, the authors first studied the basic mechanisms
in mice.
They revealed a surprising property of the population of neurons expressing the Vsx2 gene: While these neurons were not necessary for walking in healthy mice, they were essential
for the restoration of motor function after spinal cord injury.
This discovery is the result of
several phases of basic research.
For the first time, the authors were able to visualize the spinal cord activity
of patients while walking.
This led to an unexpected discovery: during this spinal cord stimulation, neuronal activity was actually reduced
during walking.
They speculate that this is because neuronal activity is selectively directed towards restoring motor function
.
To test their hypothesis, the authors developed advanced molecular techniques
.
Courtine said, "We established the first three-dimensional molecular map
of the spinal cord.
Our model allows us to observe this motor recovery process
at --- neuronal level ---- greater granularity.
"Thanks to their highly accurate model, they found that this spinal cord stimulation activates Vsx2 neurons, and these neurons become increasingly important
as this recombination process unfolds.
" Co-author Stéphanie Lacour of the Ecole Polytechnique Fédérale de Lausanne, a multifunctional spinal implant, validated their findings with an epidural implant developed in her lab.

Lacour tuned the epidural implant by adding light-emitting diodes so that it not only stimulates the spinal cord, but also inactivates
Vsx2 neurons individually through an optogenetic process.
When this method was applied to mice with spinal cord injury, the mice immediately stopped walking due to Vsx2 neuronal inactivation, but had no effect
on healthy mice.
This means that Vsx2 neurons are both necessary and sufficient
for spinal cord stimulation therapy to exert therapy and cause neural reorganization.
Lumbar spinal epidural electrical stimulation applied during neurorehabilitation remodeling the spinal cord
in humans and mice.
Image from Nature, 2022, doi:10.
1038/s41586-022-05385-7
.
"It's critical
for neuroscientists to be able to understand the specific role each subset of neurons plays in complex activities like walking," Bloch said.
In our new study, 9 clinical trial patients were able to regain some degree of motor function thanks to our epidural implant, which gives us valuable insight
into this recombination process of spinal neurons.
"This paves the way
for more targeted treatment for paralyzed patients.
" We now want to manipulate these neurons to achieve the goal of
spinal cord regeneration.
"Reference: Claudia Kathe et al.
The neurons that restore walking after paralysis, Nature, 2022, doi:10.
1038/s41586-022-05385-7