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Major breakthrough in understanding SCI

.NeuroRestore research has located the type of neuron activated and remodelled by spinal cord stimulation

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In a huge breakthrough for the understanding of spinal cord injury, scientists have identified the neuron in the spinal cord that restores walking after SCI. 

A new study by the .NeuroRestore research centre has located the type of neuron that is activated and remodelled by spinal cord stimulation, allowing patients to stand up, walk and rebuild their muscles – improving their quality of life. 

This discovery, made in nine patients, has been hailed as a fundamental, clinical breakthrough. 

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 paralysed by a SCI 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 – a research partner of medtech pioneer ONWARD – 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 neuro-rehab process was completed and when the electrical stimulation was turned off. 

This suggested that the nerve fibres used for walking had reorganised. The scientists believe it is crucial to understand exactly how this neuronal reorganisation occurs in order to develop more effective treatments and improve the lives of as many patients as possible. 

“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 reorganisation process for spinal cord neurons.”

Dave Marver, CEO of ONWARD, says: “The findings continue to build our strong knowledge base in spinal cord stimulation to help people with paralysis. 

“As a result of this study and its accompanying scientific breakthrough, ONWARD and its research partners have learned precisely where to place the epidural lead and how to program stimulation to facilitate walking. 

“This important work is enabling us to develop a therapy for people with spinal cord injury that aims to be precise, repeatable, and scalable.”

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 visualise 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 hypothesised 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.” 

Through this highly precise model, the scientists found that spinal cord stimulation activates Vsx2 neurons and that these neurons become increasingly important as the reorganisation process unfolds. 

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 reorganisation. 

Jordan Squair, who focuses on regenerative therapies within .Neurorestore, adds: “This paves  the way to more targeted treatments for paralysed patients. We can now aim to manipulate these neurons to regenerate the spinal cord.” 

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