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Nine Paralysis Patients Walk Again Thanks to Newly Identified Neurons

Two men walk with wheeled walkers.
Two Patients Walking Credit: NeuroRestore - Jimmy Ravier
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A new study has identified nerve cells that are altered in response to a spinal cord stimulation technique proven to restore walking ability in people once thought to be permanently paralyzed. The study involved restoring movement in nine patients with severe spinal cord injury before examining damage at a cellular level in a mouse population. This analysis revealed that two populations of neurons in the lumbar spinal cord were prioritized in response to the stimulation. The research is published in Nature.

Stimulation solution

Spinal cord injuries disrupt the communication systems between the brain and neurons in the spinal cord that direct movement. Over the last five years, scientists have developed systems that utilize electrical stimulation to help individuals recover from the paralysis that often results from such injuries. These interventions, which have been enhanced further in combination with motor rehabilitation, have changed lives but remain largely unexplained.

In a new paper, a research team at the Swiss Federal Institute of Technology Lausanne (EPFL) working with Jocelyn Bloch, a neurosurgeon at Lausanne University Hospital, demonstrated the effectiveness of their technique, termed epidural electrical stimulation. In a clinical trial, a further nine patients saw their walking ability immediately improve after the stimulation was switched on. Some of the patients were able to retain improved motor function even after the stimulation was silenced.

This latter finding suggests that lasting changes are being made to the function of neurons in the spinal cord. Study leader Grégoire Courtine, a neuroscience professor at EPFL, and his team decided to examine in detail what was happening in their patients’ spinal cords.

Zeroing in on recovery neurons

The team was surprised to note that overall activity in the spinal cord actually decreased in response to the stimulation, suggesting that the response was being driven through smaller subpopulations of neurons rather than an en masse effort.

To tease out the groups of neurons responsible, the team worked with mice that had received similar spinal cord injuries. They created maps of gene activity in the mice’s spinal cord neurons, allowing them to track the cells that were preferentially targeted by the stimulation treatment. “Our model let us observe the recovery process with enhanced granularity – at the neuron level,” said Courtine in a press release.

They settled on a group of excitatory lumbar interneurons, expressing a gene called Vsx2, that were critical to the mice’s restored walking ability. Interestingly, the same neurons were not needed by healthy mice to walk.

The team used advanced light-based stimulation techniques to show that when the Vsx2-expressing neurons were deactivated, mice with spinal cord injuries were no longer able to walk. Mice that had these neurons deactivated chronically were also unable to gain any initial benefit from the stimulation.

A first step towards tackling paralysis

The authors acknowledge that walking is additionally controlled by numerous neural populations throughout the brain and spinal cord; those neurons’ locations and connectivity will have to be unearthed in future research.

Nevertheless, this is an important first step in the process, 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.”

“This paves the way to more targeted treatments for paralyzed patients. We can now aim to manipulate these neurons to regenerate the spinal cord,” added study co-author and EPFL researcher Jordan Squair.

Reference: Kathe C, Skinnider MA, Hutson TH et al. The neurons that restore walking after paralysis. Nature. 2022. doi: 10.1038/s41586-022-05385-7