People with complete paralysis walk again after breakthrough nerve stimulation

Using a combination of electrical stimulation and intense physical therapy, nine people with chronic spinal injuries have restored their ability to walk.

All suffered severe or complete paralysis as a result of spinal cord damage. Incredibly, all volunteers saw improvements immediately and continued to show improvements five months later.

A recent study by researchers from the Swiss research group NeuroRestore has identified the exact nerve groups stimulated by the therapy, using mice as a starting point.

The nerve cells that orchestrate walking are located in the section of the spinal cord that runs along our lower back. Injuries to our spinal cord can disrupt the brain’s chain of signals, preventing us from walking even when these specific lumbar neurons are still intact.

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Unable to receive commands, these “walking” neurons become effectively non-functional, which can lead to permanent paralysis of the legs.

Previous research showed that electrical stimulation of the spinal cord can reverse this paralysis, but it was not clear how this happened. So neuroscientist Claudia Kathe of the Swiss Federal Institute of Technology in Lausanne (EPFL) and her colleagues tested a technology called epidural electrical stimulation in nine individuals, as well as in an animal model.

The spinal cord was stimulated by a surgically implanted neurotransmitter. Meanwhile, the patients also underwent an intensive neurorehabilitation process involving a robotic support system that assisted them while moving in multiple directions.

The patients went through five months of stimulation and rehabilitation, four to five times a week. Amazingly, all volunteers were able to take steps with the help of a walker.

To the researchers’ surprise, the recovered patients actually showed reduced neural activity in the lumbar spinal cord during walking. The team believes this is because the activity is being fine-tuned to a specific subset of neurons that are essential for walking.

“When you think about it, it shouldn’t be a surprise,” Courtine told Dyani Lewis in Nature, “because in the brain, when you learn a task, that’s exactly what you see: fewer and fewer neurons are activated” as you do improve it

So Kathe and the team modeled the process in mice and used a combination of RNA sequencing and spatial transcriptomics, a technique that allows scientists to measure and map gene activity in specific tissues, to understand which cells what were they doing

They identified a unique population of previously unknown neurons that can step up to take over after injury, found in the intermediate laminae of the lumbar spinal cord.

This tissue, made up of cells called SCVsx2::Hoxa10 neurons, does not appear to be necessary for walking in healthy animals, but appears to be essential for recovery after spinal injury, as destroying them prevent the mice from recovering. Their recruitment, however, depends on the activity.

SCVsx2::Hoxa10 neurons are “uniquely positioned” to transform information from the brainstem into executive commands. They are then transmitted to the neurons responsible for the production of gait, Kathe and her colleagues explain in their paper.

This is only one component of a very complicated chain of messaging and receiving cells, so there is still much to investigate.

But, “these experiments confirmed that the involvement of SCVsx2::Hoxa10 neurons is a fundamental requirement for recovery of gait after paralysis,” the researchers concluded.

This new understanding could eventually lead to more treatment options and may also provide a better quality of life for people with all types of spinal cord injuries.

Their research was published in Nature.

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