They identify neurons that restore the ability to walk after paralysis

Grégoire Courtine, a renowned Swiss neuroscientist at the Federal Polytechnic School of Lausanne (EPFL), has spent years researching how to get people with damaged spinal cords to walk again. His advances were demonstrated with mice in 2012, with monkeys in 2016, and with humans in 2018 and 2022, when he and his team got three paralyzed patients to walk again with electrical implants in the spinal cord.

Now, in a new study published in Nature Courtinand and your core group NeuroRestore from EPFL have identified the type of neuron that is activated and remodeled by spinal cord stimulation, allowing patients to stand up, walk and rebuild their muscles.

We showed that the improvement in motor function was maintained when electrical stimulation was turned off, suggesting that the nerve fibers used for walking are reorganized.

Grégoire Courtine, Research Leader

In previous research work, carried out in collaboration with neurosurgeon jocelyne blochthey did it nine paralyzed patients due to a spinal cord injury, he was able to walk again — with the help of walkers and crutches — after the introduction of electrical stimulation implants.

These volunteers “submitted to selective epidural electrical stimulation of the area that controls leg movement and were able to recover some of their motor function,” the authors specify.

In the new study “we demonstrate not only the effectiveness of this therapy in nine patients, but also that improvement in motor function was maintained once the neurorehabilitation process was completed and when electrical stimulation was turned off. This suggested that the nerve fibers used for walking had reorganized themselves,” says Courtine.

The authors found it crucial to understand exactly how this neural reorganization develop more effective treatments and improve the lives of as many people as possible.

The family of neurons that express the Vsx2 gene

To deepen this understanding, the team first studied the underlying mechanisms in mice. This revealed a surprising property in a family of neurons that express the Vsx2 gene: Although these neurons are not necessary for walking in healthy mice, they were essential for the recovery of motor function after spinal cord injury.

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This discovery was the culmination of several phases of fundamental research. For the first time, scientists were able to visualize a patient’s spinal cord activity as they walked. This led to an unexpected finding: during the spinal cord stimulation process, neural activity decreased while walking. The authors hypothesized that this was because neural activity was selectively targeted towards recovery of motor function.

To test their hypothesis, the research team developed advanced molecular technology. “We’ve established the first 3D molecular mapping of the spinal cord,” says Courtine. “Our model allowed us to look in more detail at the recovery process, at the neuronal level,” she says.

Using this highly accurate model, the team found that spinal cord stimulation activates Vsx2 neurons and that these neurons become increasingly important as the reorganization process unfolds.

A versatile spinal implant

Stephanie Lacour, an EPFL professor, helped Courtine and Bloch’s team validate their findings with epidural implants developed in their lab. Lacour adapted the electrical stimulation devices by adding light-emitting diodes that allowed the system not only to stimulate the spinal cord, but also to turn off Vsx2 neurons on its own through an optogenetic process.

When the system was used on spinal cord injured mice, they immediately stopped walking as a result of the neuron deactivation, but there was no effect in healthy mice. This implies that Vsx2 neurons are necessary and sufficient for spinal cord stimulation therapies to be effective and lead to neuronal reorganization.

“It is essential for neuroscientists to be able to understand the specific role that each neuronal subpopulation plays in a complex activity such as walking,” emphasizes Bloch. function thanks to our implants, gives us valuable insight into the process of reorganization of neurons in the spinal cord.”

Jordan Square, who is dedicated to regenerative therapies at Neurorestore, adds: “This paves the way for more targeted treatments for paralyzed patients. Now we can hope to manipulate these neurons to regenerate the spinal cord.”

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