Targeting key cells in the spinal cord got paralyzed patients walking again

by Amy Norton

Reporter of Health Day

WEDNESDAY Nov. 9, 2022 (HealthDay News) — In a breakthrough in the treatment of spinal cord injuries, researchers have identified nerve cells that are the key to allowing people with paralysis to walk again.

The findings come in part from nine patients who participated in an ongoing Swiss study that seeks to restore movement to people with paralysis.

All nine quickly regained the ability to stand and walk with the help of implants that electrically stimulate spinal nerves that control lower body movements.

Now the researchers report that they have identified a specific group of cells in the lower spine that appear to be necessary for this movement recovery to occur.

The hope, experts said, is that the discovery will help refine electrical stimulation therapy — and eventually help develop even more sophisticated ways to restore complex movements to people with paralysis.

In the United States alone, up to 450,000 people live with spinal cord injuries, according to the American Association of Neurological Surgeons. Roughly half of these injuries are in people younger than 30 years old, most of whom are men – with traffic accidents or violence often to blame.

Spinal cord injuries actually shut down communication between the brain and the spinal nerves located below the injury.

But these neurons are not useless – just offline. And for years, researchers have been studying epidural electrical stimulation (ECS) as a way to trigger neurons and restore movement in people with paralysis.

EES involves implanting electrodes that send electrical currents to neurons in the spinal cord. The electrodes are connected to a pulse generator that is placed in the abdomen.

EES has a 50-year history of use as a treatment for pain, said Eiman Azim, a researcher at the Salk Institute in La Jolla, Calif., who studies the mechanisms underlying human movement.

Along the way, researchers discovered that EES also affects movement. Over the past decade or so, different research teams have used EES, along with extensive physical rehabilitation, to help a small number of paralyzed patients regain some ability to stand and walk.

The Swiss team, Azim said, have been “making giant leaps” in advancing the approach in recent years.

For example, they have developed electrodes that precisely target the “dorsal root regions” of the spinal cord that control leg and trunk movements. They have also incorporated advanced technology that stimulates nerves in a pattern that more closely mimics how the brain would do the work.

The team, from the Swiss Institute of Technology and the University of Lausanne, reported their three latest patients earlier this year. The patients, all men between the ages of 29 and 41, had suffered spinal cord injuries that left them with no feeling or movement in their legs.

All underwent surgery in 2020 to have the EES mechanism implanted. The implants were paired with software that allows patients and physical therapists to set up semi-automated stimulation programs that enable a variety of movements. People can control these programs themselves, through a tablet and small remote controls that communicate wirelessly with the pulse generator.

These three patients were able to stand and walk, with support, immediately after recovering from surgery.

The Swiss team has discovered something particularly fascinating along the way: Some of their nine patients have been able to walk even with the electrical stimulation turned off—suggesting, Azim said, a “reorganization” of the neurons involved in walking.

To dig deeper, the researchers turned to lab mice to mimic many of the key features of EES in humans with spinal cord injury. They were able to zero in on a group of neurons – called Vsx2 neurons – that appear to be “necessary” to restore walking with the EES.

“Silencing” the neurons prevented lab mice from regaining their ability to walk with EES; activating the neurons restored their movement.

“This study asked, what is happening in the spinal cord during stimulation?” Azim said. “It’s a big black box.”

Dr. Greg Nemunaitis, director of spinal cord injury rehabilitation at Cleveland Clinic in Ohio, called the nine patients’ functional recovery “fantastic.”

He also said that the discovery of “recovery-organizing neurons,” while in mice, is “a first step in understanding and increasing function in humans until the ‘cure’ is found.”

Azim said that in the short term, the findings of these key neurons could help further refine the EES.

Looking to the future, he said, a greater understanding of how EES contributes to movement recovery could help develop even more sophisticated treatments. Technology is advancing to the point where it may eventually be possible to safely access the spinal cord and “rebuild” damaged circuits, Azim said.

“This is not a dream,” he said.

The results were published online in November. 9 in the diary The nature.

More information

The American Institute of Neurological Disorders and Stroke has an overview of spinal cord injuries.

SOURCES: Eiman Azim, PhD, associate professor, Salk Institute for Biological Studies, La Jolla, Calif.; Greg Nemunaitis, MD, director, spinal cord injury rehabilitation, Cleveland Clinic, and professor, Case Western Reserve University School of Medicine, Cleveland, Ohio; nature, Nov. 9, 2022, online

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