The neurons that restore walking after paralysis

Scientists in Switzerland identified the neuron in the spinal cord that restores walking after spinal cord injury

A new study by scientists at the .NeuroRestore research center hasidentified the type of neuron that is activated and remodeled by spinalcord stimulation, allowing patients to stand up, walk and rebuild theirmuscles – thus improving their quality of life. This discovery, made innine patients, marks a fundamental, clinical breakthrough. The study waspublished today in Nature.


In a multi-year research program coordinated by the two directors of  .NeuroRestore – Grégoire Courtine, a neuroscience professor at EPFL, and  Jocelyne Bloch, a neurosurgeon at Lausanne University Hospital (CHUV) – patients who had been paralyzed by a spinal cord injury and who underwent  targeted epidural electrical stimulation of the area that controls leg movement  were able to regain some motor function. In a new study by .NeuroRestore  scientists, appearing today in Nature, not only was the efficacy of this therapy  demonstrated in nine patients, but the improved motor function was shown to  last in patients after the neurorehabilitation process was completed and when  the electrical stimulation was turned off. This suggested that the nerve fibers  used for walking had reorganized. The scientists believe it was crucial to  understand exactly how this neuronal reorganization occurs in order to develop  more effective treatments and improve the lives of as many patients as  possible.

Vsx2 neurons reorganize to restore walking

To arrive at this understanding, the research team first studied the underlying  mechanisms in mice. This revealed a surprising property in a family of neurons  expressing the Vsx2 gene: while these neurons aren’t necessary for walking in  healthy mice, they were essential for the recovery of motor function after spinal  cord injury.

This discovery was the culmination of several phases of fundamental research.  For the first time, the scientists were able to visualize spinal cord activity of a  patient while walking. This led to an unexpected finding: during the spinal-cord  stimulation process, neuronal activity actually decreased during walking. The  scientists hypothesized that this was because the neuronal activity was  selectively directed towards recovering motor function.

To test their hypothesis, the research team developed advanced molecular  technology. “We established the first 3D molecular cartography of the spinal cord,” says Courtine. “Our model let us observe the recovery process with  enhanced granularity – at the neuron level.” Thanks to their highly precise  model, the scientists found that spinal cord stimulation activates Vsx2 neurons  and that these neurons become increasingly important as the reorganization  process unfolds.

A versatile spinal implant

Stéphanie Lacour, a fellow EPFL professor, helped the research team validate  their findings with the epidural implants developed in her lab. Lacour adapted  the implants by adding light-emitting diodes that enabled the system to not just  stimulate the spinal cord, but also to deactivate the Vsx2 neurons alone  through an optogenetic process. When the system was used on mice with a  spinal cord injury, the mice stopped walking immediately as a result of the  deactivated neurons – but there was no effect on healthy mice. This implies  that Vsx2 neurons are both necessary and sufficient for spinal cord stimulation  therapies to be effective and lead to neural reorganization.

“It’s essential for neuroscientists to be able to understand the specific role that  each neuronal subpopulation plays in a complex activity like walking,” says  Bloch. “Our new study, in which nine clinical-trial patients were able to recover  some degree of motor function thanks to our implants, is giving us valuable  insight into the reorganization process for spinal cord neurons.” Jordan Squair,  who focuses on regenerative therapies within .Neurorestore, adds: “This paves  the way to more targeted treatments for paralyzed patients. We can now aim to  manipulate these neurons to regenerate the spinal cord.”

Press kit (images, animations): https://go.epfl.ch/Vsx2

Contact for the media: Emmanuel Barraud, EPFL spokesperson,  emmanuel.barraud@epfl.ch, +41 21 693 21 90

Jimmy Ravier