Walking again after paralysis: Early study suggests stimulation could jolt spinal cord back to life

After a traumatic motorcycle collision in 2017, Michel Roccati was left completely paralyzed from the waist down. He couldn’t have imagined that a few years later, he would be walking through the streets of Lausanne, Switzerland.

Roccati is one of three men who has had his motor function restored — able to stand, walk, swim, and cycle again — with electrical stimulation of key spinal cord nerves that control lower-body movements.

The first-in-man study included three participants between the ages of 29 and 41 who had a traumatic thoracic spinal cord injury due to motorcycle collisions. All of them were several years out from their injuries and had stabilized to a point of no movement or sensation in their legs, and they had at least 6 centimeters of healthy spinal cord below their injury.

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Previous studies have shown stimulating an injured spinal cord with epidural electrical stimulation (EES) can, with time, help restore mobility in some people with paralysis, but a paper published in Nature Medicine on Monday goes a step further. The findings suggest people with complete paralysis could regain a broader range of motion within days if dormant spinal nerves that mediate leg and upper-body movement are reengaged with a personalized device.

“We are much more precise, effective, and rapid to deliver the therapy,” said senior author Grégoire Courtine, the International Paraplegic Foundation chair in spinal cord repair at the Center for Neuroprosthetics and the Brain Mind Institute at the Swiss Federal Institute of Technology in Lausanne.

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Eellan Sivanesan, director of neuromodulation in the Division of Pain Medicine at Johns Hopkins School of Medicine, agreed that the speed of motor function restoration was noteworthy. “Previous reports have described months of intensive neurorehabilitation alongside EES in order to restore motor function. The shortened time to treatment effect in the current study could allow more widespread adoption of this treatment (if pending clinical trials are supportive),” he told STAT in an email. Sivanesan was not involved with the new study.

Roccati, one of the study subjects, has done rehabilitation therapy for over a year and, with stimulation, can stand for almost two hours. He can move around using a walker for body support. He has regained some sensation in his legs with the therapy, and can feel his lower body making contact with the ground and his muscles contracting when he goes for his daily walks, he told reporters during a recent news conference. Using a tablet, he controls stimulation, and is able to turn it on and off based on what activity he is doing.

Roccati learned about the stimulation research project from a speaker at a brain conference in Italy not long after his injury. He reached out to the team and, after two years, was enrolled in the study. He received the spinal implant in August 2020 and could walk with body support on the first day of stimulation, 11 days after the procedure. “I was able to see my legs moving, and it was very emotional,” he told reporters.

He stayed in Lausanne for nine months, training everyday, and then continued rehabilitation at home. “I see the improvement every day,” he said.

All three study participants could take as many as 300 steps (independently, with body support) within days of starting stimulation, researchers report in the paper.

Dorsal roots feed information into the central nervous system and the brain. By mapping out how motor neurons fire in the spines of healthy, non-paralyzed people while doing various motor activities, the researchers were then able to determine how to stimulate those same nerves in the paralyzed patients. Another recent study also pointed toward bundles of neurons in dorsal roots as an area ripe for exploration when it comes to spinal cord injuries.

Courtine and his team targeted these roots in the lower back and tailbone by placing a paddle-shaped device embedded with electrodes directly on the spinal cord, aligning electrodes with nerve roots. The adapted paddle, fabricated by biotechnology company ONWARD Medical, is longer and wider than transitional leads, in order to reach those key nerve targets. The paddle connects to a Medtronic device, typically used for deep brain stimulation, in the patient’s abdomen. (Courtine and other researchers hold several patents related to the technology used in the research, and several are shareholders of ONWARD Medical.)

Software programmed into a tablet and connected to a simple clicker allowed participants to choose what type of stimulation they wanted based on what activity they were doing (walking, standing, etc.)

Researchers began with a generic model of the stimulation device — repurposed from its original use, for treating pain, in order to target the right spinal cord segment — and then adapted it for each participant, Courtine said. Once Jocelyne Bloch, a neurosurgeon at Lausanne University Hospital, implanted the stimulator, the devices were tested and adjusted to account for the variability in spinal cord length, nerve positioning, and other factors.

Courtine and Bloch dream of one day building a “library” of electrode arrays for surgeons to choose from depending on the patient’s injury, their spinal cord length, etc.

The combination of state-of-the-art technology and known physiological principles is “unprecedented” in studies of people with severe paralysis, said Reggie Edgerton, who oversaw some of Courtine’s postdoctoral work at the Brain Research Institute at the University of California at Los Angeles. “The ability to integrate all of these advanced technologies in a human subject over a period of months is unique and impressive. These data also demonstrate the complexity of the problem in regaining motor function after severe paralysis and thus the challenges before us.”

There are still improvements to be made. While participants could stand and step within a day of receiving stimulation, their gait was still clumsy and nonfluid. Body weight support was another skill that had to be rehabilitated after surgery, researchers said.

“The stimulation really reactivates the spinal cord,” but motor function must be regained, Courtine said. Animal studies suggest the spines of younger humans might bounce back more effectively with a boost from stimulation, he said. And there is reason to believe that electrical stimulation could help more patients if used early on after a spinal cord injury, in concert with the body’s natural repair mechanism, the researchers said.

One limitation of the ONWARD paddle used in the new research is its insertion into the body is more invasive than that of a typical spinal cord stimulation device, which can usually be implanted through a needle, said Sivanesan. The new paddle is implanted during a surgery that entails cutting down to the spinal cord and attaching the paddle by anchoring it to ligaments. The surgical aspect could “limit the number of physicians readily able to apply the treatment,” Sivanesan said.

The next step will be validating the results in a large-scale trial in the United States and Europe in hopes of making this form of spinal stimulation an accessible treatment that will be reimbursed by insurance companies, Courtine said. ONWARD also wants to make the stimulation device connectable to a phone or wearable, such as an Apple Watch.

“The challenge for the future is not only improving these approaches and developing other approaches, but to manage the application of these interventions so that many individuals can benefit, given that the access to high levels of technology may be an impediment,” Edgerton told STAT.

Source: STAT