About a decade ago, a 25-year-old Oregon man named Rob Summers walked again, taking steps on a treadmill six years after a drunk driver paralyzed him from the chest down. Summers, as Popular Science reported in 2011, was among the first patients with paralysis to receive an experimental electrical device: a stimulator that restored his ability to walk after two years of training.
Placing an electrode array in patients’ lower backs, researchers have found, can activate spinal circuitry in a way that repairs motor function. The needle-like implants deliver electricity directly to specific locations along the backbone. Exactly why these pulses restore walking, though, is something of a neurological mystery. A spinal cord injury can interrupt the connection between a person’s extremities and their brains, leaving them unable to move their limbs in some cases. For stimulation to work then, cells within the spinal cord’s own nerve system must reorganize in a way to process electrical signals, as the scientists leading these trials have hypothesized. If doctors can pinpoint how and why, they could apply the therapy to more kinds of paralysis, and someday, maybe even regenerate damaged cells.
Gaps in neuroscience
In recent years, clinicians have continued to test spinal implants, in some cases refining the stimulators’ design. A study published on November 9 in the journal Nature provides a clue to what changes in the vertebrae: Signals from the electrodes can excite a certain type of neuron in the nerves surrounding the spinal cord, as an international team of scientists found by examining mice. They note these neurons typically aren’t needed to help the rodents take steps—the cells only become activated for walking after the electrical stimulation treatment. The study also confirmed that the stimulators restored walking in nine people with chronic paralysis, whose spines were imaged via PET scan to measure cellular activity.
Identifying these cells “is an important step towards gaining a better understanding of how the spinal cord controls movement” and how this therapy “improves walking function after a severe spinal cord injury,” says Ursula Hofstöetter, a professor at the Medical University of Vienna who studies the way our bodies control locomotion, but wasn’t involved in the new report. It might one day lead to drugs that target these neurons, too, she adds.
Mapping the cells that become activated and the genes they express—in the case of the mouse model, the researchers pinpointed a gene in the neurons called Vsx2—can show scientists how spinal cords reorganize cell networks after injury. That’s the principle behind epidural electrical stimulation, the technique that helped Summers walk, as well as nine patients in the new study. (“Epidural” refers to the space between the spinal cord and backbone; it’s perhaps best known as the site where anesthesiologists may administer numbing medication to people in labor.)
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An unusual pattern occurs in the spinal nerve systems of patients who receive this stimulation: Their movement may improve even when the stimulators are turned off. What’s more, the overall level of cell activity in the spinal networks appears to decrease, says study author Jordan Squair, a postdoctoral scientist at the Swiss Federal Institute of Technology. Essentially, he says, the spines are becoming “more efficient”—unlike at the start of rehabilitation, they no longer need to activate a whole bunch of cells to create movement.
That led Squair and his colleagues to investigate which neurons wind up taking the lead. After a spinal cord injury, healthy circuits become disrupted, says Michael Oh, a neurosurgeon at the University of California, Irvine. The activated cells identified in this study are probably intermediaries between the neurons responsible for sensation and those that govern motion, smoothing out that disorganization and streamlining firing circuits.
Squair believes these kinds of neurons govern more functions than walking, too. A 2021 Nature paper by many of the same authors as the new research showed epidural electrical stimulation can help regulate the blood pressure of patients with paralysis.
In case studies, epidural electrical stimulation has been so successful, Hofstöetter says, the recovery for people living with severe spinal cord injury reached levels “that were previously deemed impossible.”
What’s in a stimulator
In most instances, including for six patients in the more recent Nature study, the implanted electrode arrays were repurposed from machines originally designed to treat neuropathic pain. But three people in this report had an experimental device, under commercial development by Onward Medical and based on research by the Swiss company NeuroRestore, of which Squair is a part.
Because this device was tailored to help revive function in patients with paralysis, Squair says the stimulator can restore sensation more quickly than older implants. “To activate the muscles that you want to activate, you need to target the right spots on the spinal cord,” he says. “The leads that have been originally designed for pain don’t provide the ability to do this.” The stimulators can also be programmed to deliver signals timed to the pattern of locomotion.
Hofstöetter agrees that, compared with versions meant for pain relief, this is a “more sophisticated, high-end technological” implant. But, she notes, no study “has specifically investigated whether such level of technological complexity would be” better than conventional devices.
No matter the device—there are about a half-dozen companies working on these kinds of spinal stimulators, Oh points out—the effect is not like turning on a switch. As the Nature report describes, for the patients with chronic paralysis to walk, it required five months of physical therapy, with one- to three-hour sessions up to five times a week. Restoration of function may also mean training for specific motions.
“Getting people out of wheelchairs and walking independently is a miracle,” Oh says. In the current study, all nine participants could walk, some independently and others with assistance. But this stimulation is not a panacea for paralysis, he notes: It cannot repair the ability to run, dance, or kick.
Not every participant responds to stimulation in the same way. And, taking a broad view of spinal cord stimulators, the surgically implanted devices used for long-term pain relief have occasionally harmed patients. An Associated Press investigation found that 80,000 incidents had been flagged to the Food and Drug Administration from 2008 to 2018.
The future of treating paralysis
As much as neurosurgeons and scientists praise the results that stimulators have shown in experimental settings, for the past decade, access to the implants has been generally limited to participation in small trials. Hofstöetter estimates that, across the planet, fewer than 50 people with spinal cord injuries have electrical stimulators. Yet most people with spinal cord injuries could be helped, she suspects, as long as the neuronal networks in the lower part of the spine, the lumbar region, are intact. More work is needed to bridge the gap between proof-of-concept studies and the thousands of people living with paralysis or motor disorders, she says.
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A small clinical trial, called STIMO, is underway, led by researchers in Switzerland; the nine participants from the Nature study are enrolled in that trial. But larger tests would be needed for the FDA or other regulators to permit these devices to be used outside experimental settings. “There needs to be a pivotal clinical trial—that’s the first step that needs to happen,” Squair says.
Some patients with paralysis also say they would prefer stimulation to address functions other than walking, such as control over their bowels, arms, or sexual organs. Ongoing research includes stimulation that targets the bladder, and other studies involve the upper spine in an attempt to improve hand function. To walk again may be just the start, but before that, more mysteries remain. The exact way this motor function is restored continues to be a puzzle. Thanks to this neuron study, Oh says, we have a target—but we still don’t know the mechanism.
