Electrical stimulation helps paralyzed people walk again

Originally written by Dyani Lewis

Detailed gene activity profiles give many spinal cord injury patients hope to receive precision treatment
.

Neuroscientists have identified nerve cells that help paralyzed people walk again, opening up the possibility of targeted therapies that could potentially benefit more people with spinal cord injuries [1].

Severe spinal cord injuries disrupt the brain's connection to the network of nerve cells in the lower spine, which controls our ability to
walk.
In 2018, Grégoire Courtine, a neuroscientist at the Ecole Polytechnique Fédérale de Lausanne, and his colleagues showed that releasing electrical impulses to the nerves of the lower spine — a technique called epidural electrical stimulation (EES) — combined with intensive training, could allow people with such spinal cord injuries to walk again [2].

All three participants in one clinical trial improved from severe or total motor paralysis and minimal sensation in the legs to being able to walk on their own or with the help of walkers or crutches
.
Two other teams reported similar results in 2018 [3,4].

Remodeling specific neurons allows partial recovery
from spinal cord injury.
Source: Steve Gschmeissner/SPL

Now, Courtine's team has expanded that work
even further.
They demonstrated that the system also works for patients with
complete loss of sensation in their legs.
The research team said in Nature that nine subjects in the same trial — three of whom were totally paralyzed and unconscious in their legs — regained the ability to
walk through EES treatment combined with training through spinal implants.
Five months after the start of the trial, all participants were able to bear their own weight and walk while remaining steady
with the help of a walker.

4 people no longer need to activate EES to walk
.
This sign of continued recovery suggests that electrical stimulation activates the remodeling of spinal cord neurons, remobilizing the body's motor network
.

Marc Ruitenberg, a neurologist at the University of Queensland in Australia who specialises in spinal cord injuries, said: "This holds great promise
for people with spinal cord injuries.
”

Inhibited activity

Courtine's team also identified neurons
that enhance rehabilitation.
Counterintuitively, if EES in the human body is activated, nerve cell activity at the stimulation site is reduced
.
The research team used this clue to conduct a study
from start to finish.
First, the research team simulated the entire treatment process with mice—from injury to electrical stimulation to training with robots that assisted stabilization
.
The end result is similar
to that of human trials.

Next, the team measured the gene activity of thousands of individual neurons in mouse spinal cord tissue samples, and based on this, they created an ultra-detailed map
of the lower spinal nerve cell types.
They then used a machine learning algorithm to look for mouse neurons that showed changes in gene activity in preparation for EES-assisted rehabilitation, and these changes needed to be consistent with
those observed in the walking ability of human subjects.

The algorithm found that a subset of excitatory interneurons, which are nerve cells
that connect motor neurons and sensory neurons, seemed to meet the criteria.
When Courtine's team silenced the cells in the injured mice, they found that EES could no longer help the injured mice walk.

Courtine believes that the overall decline in neuroactivity at the site during rehabilitation reflects the process of
learning.
"If you think about it, it's not surprising," he says, "because for the brain, that's exactly what happens when you learn a task — when you learn it, fewer neurons are activated
.
" ”

The future of work

No technique currently collects such direct evidence
from humans.
But Eiman Azim, a neuroscientist at the Salk Institute for Biological Research in California, believes that the same neurons may have caused the effect because the spine structures of different vertebrates are very similar, including humans and mice
.

Azim says a detailed understanding of spinal circuits could eventually allow neuroscientists to directly manipulate the activity of specific neurons in other therapies, such as gene therapy
.
Ruitenberg said stem cell therapy may be able to replace key neuronal populations damaged in spinal cord injuries in the future
.

Courtine and colleagues also used EES to restore the monkeys' arm movement and grasping ability [5].

A team at the University of Washington conducted the same experiment on six patients with spinal cord injuries using a non-invasive electrode skin patch attached to the neck [6].

While it's amazing to see people with spinal cord injuries walk again, Ruitenberg says walking is sometimes not the biggest need
for these people.
Loss of bladder control, bowel control, and sexual function can also seriously affect quality of life
.
"People are curious to see if this technology can also improve functionality in these areas
," he said.
”

Courtine says identifying the nerves responsible for these functions is one of his next goals, as detailed molecular maps
are now available.
HE ALSO FOUNDED ONWARD IN THE NETHERLANDS, SPECIALIZING IN COMMERCIALIZING
THE TECHNOLOGY.
The company will begin recruiting 70-80 subjects
in the United States in 2024.

References:

1.
Kathe, C.
 et al.
 Nature https://doi.
org/10.
1038/s41586-022-05385-7 (2022).

2.
Wagner, F.
B.
 et al.
 Nature 563, 65–71 (2018).

3.
 Gill, M.
L.
 et al.
 Nature Med.
 24, 1677–1682 (2018).

4.
 Angeli, C.
A.
 et al.
 N.
Engl.
J.
Med.
 379, 1244–1250 (2018).

5.
Barra, B.
 et al.
 Nature Neurosci.
 25, 924–934 (2022).

6.
Inanici, F.
, Brighton, L.
N.
, Samejima, S.
, Hofstetter, C.
P.
& Moritz, C.
T.
 IEEE Trans.
Neural Syst.
Rehabil.
Eng.
 29, 310–319 (2021).

The original article was published in the November 9, 2022 news section of Nature as Electrical stimulation helps paralysed people walk again — and now we know why

© nature

doi: 10.
1038/d41586-022-03605-8

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