Nine paralyzed patients regained the ability to walk, and scientists discovered the neurons responsible for walking

Scientists now have a better understanding
of how our bodies respond to spinal cord injuries and the specific cells that may guide spinal cord recovery.
In a study published Nov.
9 in the journal Nature, researchers followed nine paralyzed patients who received an electrical stimulation regimen who regained the ability to walk and compared
their findings to mice that received similar treatments.
In animal models, the team found two groups of nerves that appear to command the rewiring
of connections between nerve cells after injury.
If these neurons play the same role in humans, this could lead to more targeted treatments
for spinal cord injuries.

In 2018, scientists first recognized that stimulating nerves near the site of injury — a process known as epidural electrical stimulation (EES) — could relieve pain after a spinal cord injury and restore their ability to
walk when combined with intensive physical therapy.
But experts say that although this approach is one of the few with significant clinical effects, it is never entirely clear how EES works
.

To explore the mechanistic basis of treatment, Grégoire Courtine, a neuroscientist at the Swiss Federal Institute of Technology in Lausanne, who was part of the 2018 study, followed 9 patients who underwent a 5-month EES, physical therapy and rehabilitation program
.
Six patients retained some leg sensation after their injuries, but three of them were completely paralyzed from the waist down
.
Throughout the treatment, the team mapped the activity of nerve cells in each patient
.
As each person progresses and regains the ability to walk, the level of nerve activity near the injured site decreases
.
However, this was no surprise
to the team.
Courtine told Nature that this reflects what happens
in the brain during learning.
"When you learn a task, that's what you see — when you do better, fewer and fewer neurons are activated
," he said.
Co-author Jocelyne Bloch of the University of Lausanne notes that after a spinal cord injury, the body has a lot of "chaotic activity.
"
The rehabilitation process "organizes the network of cells, and you actually increase the activity of a particular type of cell while all the other cells are not activated
.
" ”

Taken together, the findings suggest to the team that there may be a subset of neurons responsible for coordinating a person's recovery
.
The scientists decided to study the idea in mice, inducing spinal cord injuries in animals and simulating their recovery process in an attempt to reproduce their findings
.
When they applied a murine version of EES to mice with hindlimb paraplesis, they saw the same reduced
activity seen in humans.

Next, the researchers measured gene expression in populations of neurons in mouse spinal cord tissue, classifying neurons into subsets
based on their expression profiles.
Using machine learning algorithms, the team was able to map changes
in gene expression corresponding to different stages in the human patient's recovery trajectory.

Specifically, the algorithm identified two subpopulations of excitatory interneurons (nerve cells that connect motor neurons and sensory neurons) that expressed the genetic markers Vsx2 and Hoxa10 as potential drivers of recovery in animals
.
When the scientists applied optogenetics to inactivate these cells, the mice lost the ability to walk, and only when the cells were activated could they regain the ability to
walk.
In mice without spinal cord injury, silencing the cells did not have any effect, suggesting that these cells were only critical
for exercise after injury.

Marc Ruitenberg, a neuroscientist at the University of Queensland who studied spinal cord injuries who was not involved in the study, said the findings gave people with spinal cord injuries "incredible"
.

Other researchers are more cautious
in their explanations.
Eiman Azim, a neuroscientist at the Salk Institute for Biological Research in California, told Nature that we don't yet have the technology to manipulate human neurons in the same way that we manipulate mouse neurons, so it's not yet possible to gather direct evidence that EES induces the same changes
in humans.
Still, he says, he suspects it may have been the same neurons that led to the effects the team saw in patients, because vertebrates have very similar
vertebrate structures.

Courtine has launched a startup called ONWARD to commercialize the technology and plans to recruit patients for new trials
in the U.
S.
in 2024.
Some members of the team, including Courtine, who had previously used EES to restore arm movement and grip strength in non-human primates, said Courtine said he was interested in seeing if EES could regain other functions lost due to injury, such as bladder and bowel control, or the ability to
perform sex.