Nature: Allowed 9 paralyzed patients to regain the ability to walk, and now the cause is finally understood

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SourceLilac Academic

As early as 30 years ago, preclinical and clinical studies showed that epidural electrical stimulation (ESS) on the lumbosacral spinal cord restored the ability
to walk in patients with spinal cord injury.
But this requires the assistance of several physical therapists, months of intense training, and extremely limited success
.
Translating these complex, rare cases into a universally applicable treatment is a huge challenge
.

Dr.
Grégoire Courtine of the Swiss Federal Institute of Technology in Lausanne and Jocelyne Bloch, a neurosurgeon at the University Hospital of Lausanne, have developed a targeted neurotechnology that uses electrical stimulation to reactivate spinal cord neurons, allowing multiple chronic paraplegics to regain the ability to
walk.
However, the biological mechanism behind this treatment technology remains unclear
.

On November 9, 2022, the team of Grégoire Courtine et al.
at the Ecole Polytechnique Fédérale de Lausanne published a research paper in Nature entitled: The neurons that restore walking after paralysis.

The study helped nine patients with severe or complete paralysis due to spinal cord injury successfully regain the ability to walk through the use of epidural electrical stimulation (EES) and identified the types
of neurons that play a key role in the spinal nerve remodeling process.

This study advances our understanding of how to regain mobility after paralysis and marks a fundamental clinical breakthrough
.

In the clinical trial, the research team recruited nine participants
who were severely or completely paralyzed due to spinal cord injury.
Participants received five months of epidural electrical stimulation (EES) treatment
.
Over time, participants' ability to bear weight, stand, and walk improved
dramatically.

Video: Patients with spinal cord injuries undergoing EES rehabilitation regain the ability to walk

Continued recovery of walking ability suggests that EES rehabilitation has reshaped the patient's spinal cord
.
The authors speculate that this remodeling would be reflected in the activity
of neurons involved in the walking process.

The spinal cord is made up of
many different cell types that are highly interconnected.
To explore cell types that might be involved in EES therapy-mediated recovery, the research team developed a mouse model that replicates many key features of the human EES therapy-mediated neurorehabilitation process.

The authors obtained high-resolution single-cell maps of gene expression at several stages of rehabilitation by snRNA-seq sequencing and spatial transcriptomics from 61 spinal cord section single cells to capture detailed changes
in gene expression that occur during EES therapy-mediated recovery from paralysis.
The spatial location
of key neuronal subsets was then validated using multiplex RNAscope.

EES rehabilitation reshapes the spinal cord in humans and mice

By combining the above model with the molecular map, the authors identified a class of excitatory neurons activated by EES, SC^Vsx2::Hoxa10, which are one of the
specific subpopulations of vertebrate brainstem and spinal cord V2a neurons.
These neurons are important for restoring the ability to walk after spinal cord injury, but are not necessary
for individuals without spinal cord injury.

SC^Vsx2::Hoxa10 converts incoming information from the motor region of the brainstem into executive commands and delivers it to ventral neurons
responsible for the ability to walk.
Silencing these neurons impairs electrical stimulation-mediated walking recovery after spinal cord injury, while activating this group of neurons even in the absence of EES treatment improves walking
in paralyzed patients.