LOS ANGELES — There are tiny rat treadmills in the lab. And jars of Nutella, also for the rats. There are video cameras, heaps of electrodes, and instruments for slicing frozen brain tissue.
And in the center of it all: Reggie Edgerton, a 75-year-old physiologist who has spent four decades on a stubborn quest to prove, in the face of scientific ridicule, that severed spinal cords can be jolted back to life — and that paralyzed patients need not be paralyzed forever.
Now, he’s got the data to prove it.
“Spinal cord injury may no longer mean a lifelong sentence of paralysis,” said Dr. Roderic Pettigrew, director of the National Institute of Biomedical Imaging and Bioengineering, which is funding some of Edgerton’s research.
Using currents of electricity to jump-start injured spinal cords, Edgerton and his colleagues have given nearly a dozen paralyzed men, including a college baseball star and a polar explorer, the ability to move their own limbs. The men have been able to once again control their bladders and bowels, function sexually, stand upright — and with assistance, take steps.
The history of paralysis research is littered with overhyped promises and false hopes. But many physicians and patient advocates say Edgerton’s work is one of the first approaches that may actually help large numbers of patients in the near future, particularly those with fairly recent injuries.
“It’s spectacular,” said Susan Howley, who oversees research on paralysis at the Christopher and Dana Reeve Foundation. “For the first time ever, there really is hope.”
The foundation has poured more than $120 million into research over the years, and Howley has seen many promising ideas fail. But she can’t wait to launch an upcoming trial of Edgerton’s technique, which requires implanting a small medical device, about the size of a French fry, near the spinal cord, along with a battery and electronics unit. The device, made by Medtronic, sends out small amounts of electrical current. It’s approved by federal regulators to control pain, but Edgerton found it could be used to spark a damaged spinal cord back into service.
The Reeve Foundation plans to test the device in 36 paralyzed men and women in hopes of speeding it into widespread clinical use for the tens of thousands of people paralyzed by spinal cord injury. The tests will likely focus on patients injured within the past two or three years.
Edgerton’s most important insight grew out of his refusal to accept the deeply held consensus that the spinal cord is merely a humble messenger, carrying signals between the brain and the limbs like a telephone line.
Instead, he has come to see the spinal cord as smart — an organ that can, like the brain, process information, generate patterns, adapt, and learn, even after being injured.
By stimulating injured cords with electricity, Edgerton has shown he can harness their extraordinary ability to control some automatic functions, including stepping, once thought to be the exclusive province of the brain. In a surprise twist, he discovered that the stimulation somehow restores patients’ ability to voluntarily move their limbs as well — a finding that turns a century of thinking about spinal cord injury on its head.
“The spinal cord has always been the Rodney Dangerfield of the nervous system,” said Edgerton, a professor at the University of California, Los Angeles.
“That’s just hogwash.”
Photo by Kendrick Brinson
Curiosity and the cat
Edgerton’s groundbreaking work on paralysis all started with questions about a cat.
As a young professor of kinesiology in the ’70s, Edgerton took a sabbatical in Sweden to study with neurophysiologist Sten Grillner, who studied locomotion in cats that had their spinal cords severed at birth. When placed on a moving treadmill and given a dose of L-Dopa, the drug used to treat Parkinson’s disease, the paralyzed cats could walk.
Grillner hypothesized that the cats’ paws were transmitting information to the spinal cord — perhaps the sensation of holding up weight. The spinal cord then apparently generated the patterns needed to move the cats’ legs — without any help from the brain.
Edgerton was amazed.
“I wondered,” he recalled during an interview in his tidy, book-lined office, “could you retrain injured adults? It was all I wanted to work on.”
When he returned to UCLA, it took Edgerton’s team decades to get the same success with cats that had their spinal cords severed as adults, rather than as kittens, which, like infants of any species, have more flexible nervous systems.
He then turned to rats, which are easier to work with, expecting they’d respond the same way. (The experimental apparatus at his lab includes miniature treadmills and little vests to support the rats’ tiny torsos so they can walk using only their hind legs.)
It didn’t work. The injured rats just couldn’t walk.
A tall, courtly man with a neatly trimmed goatee and flowing silver hair, Edgerton speaks slowly, with a soft North Carolina drawl. His left hand is slightly undersized and weakened from the polio he suffered as a child. But this childhood injury is not what drives his work. Instead, it is his relentless curiosity.
And an absolute refusal to give up.
And so, Edgerton kept at it. His lab experimented with different ways to stimulate the rats’ broken spinal cords — and at last, years later, got them to walk. It wasn’t a Eureka moment; the methodical scientist calls it more of a “Eureka five-year event.”
The next logical step, Edgerton thought, would be helping paralyzed patients.
The problem was, no one believed him. Many scientists dismissed Edgerton’s results outright or attributed the rats’ stepping to simple reflexes. Few thought the animal results could apply to humans. Studying the spinal cord was an academic dead end — considered “the graveyard of neurobiology,” Edgerton said.
“He experienced scientific persecution. The clinical community was just laughing at him,” said Richard Lieber, the chief scientific officer of the Rehabilitation Institute of Chicago.
Edgerton still had his faculty position at UCLA. But he couldn’t get any serious funding for his research. It was too improbable. The National Institutes of Health turned down several grant proposals.
Edgerton kept going because he found the basic science so fascinating. (Colleagues credit him with making a half-dozen seminal discoveries about the architecture of muscles and how they work with neurons.)
Though he does have NIH funding now, he still credits a $2,500 grant from Easter Seals for keeping his project going at a low point.
“If you read the textbooks in neurology, no scientist in their right mind would have tried to do what Reggie did,” Lieber said. “Everyone said it wouldn’t work.”
But Edgerton didn’t listen. “Looking back on it, it’s lucky I was not trained as a neurologist because then I would have been steeped in the dogma,” said Edgerton, a Los Angeles Dodgers fan and former swim coach trained in exercise physiology. “But I didn’t even know of the dogma. I just knew what the science told me.”
One person who took quickly to Edgerton’s contrarian view of the spinal cord was the actor Christopher Reeve. In 2000, Reeve visited Edgerton’s lab and was helped onto a treadmill — a thrilling, and literally dizzying, experience for someone who’d been in a wheelchair since a 1995 horseback riding accident. Reeve died in 2004.
Edgerton, who now serves on an advisory panel for the Reeve Foundation, displays flashes of anger when he talks about the needs of paralyzed patients. Too often, he said, they’re ignored. “No one wants anything to do with them,” he said. “They have it pretty tough.”
Photo by Kendrick Brinson
‘A series of small cures’
By 2009, Edgerton had enough animal data to test his technique in paralyzed patients. He launched the human work with the help of a postdoctoral student named Susan Harkema, who now runs her own lab at the University of Louisville where she’ll carry out the Reeve Foundation trials.
Their very first experiment worked.
Rob Summers was a former Oregon State pitching star who became completely paralyzed after a 2006 hit-and-run accident, but retained some ability to feel his limbs. After receiving Edgerton’s implant, he was able to stand the very first time it was turned on. After training, he learned to flex his limbs on command — something that wasn’t expected at all.
Harkema still jokes about the curse words she uttered when Summers moved a toe on his own for the first time. Even the unflappable Edgerton was shocked.
While the finding, published in the Lancet in 2011, was received enthusiastically, critics were quick to point out that the study had just one participant — and the findings might be spurious, related to some quirk of Summer’s injury or possible only because his spinal cord was not completely severed.
In a 2014 article in Brain, Edgerton’s group reported that three additional patients, including two with complete paralysis — no ability to move or feel sensory information below their injuries — could all stand and take steps after the treatment. (Edgerton is quick to point out that none of his patients have mastered the complexities of walking; they have only taken steps with assistance.)
With training and practice, the patients’ leg movements grew stronger and more accurate. One welcome result was completely unexpected: All four men reported increased control of their bladders and bowels as well as some return of sexual function. They even reported that they had regained the ability to sweat — which is typically lost with paralysis.
And those physiological changes remained when they turned off the electric spinal cord stimulation.
Such gains may seem modest compared with the ability to fully walk again, but they greatly increase quality of life for those in wheelchairs. Howley, of the Reeve Foundation, calls the treatments “a series of small cures.”
Summers credits the procedure with changing his life: He’s been able to discard dozens of prescriptions.
In a separate study, published in December in the Journal of Neurotrauma, Edgerton’s team used external devices, rather than costly implants, to send mild electrical currents to the spines of five completely paralyzed men. They, too, were able to move their legs voluntarily with the stimulation on and even after the stimulation had stopped.
Because the patients responded so quickly, Edgerton does not think the treatment spurred the growth of replacement nerve cells. Rather, he thinks the stimulation helped “remind” the spinal cord to perform its job and awakened dormant connections between the brain and limbs.
The logical conclusion? “Complete” spinal cord injuries — where the patients cannot move or sense anything below their injuries — may not be that complete after all. Edgerton and others are starting to use a new term, “discomplete,” to indicate that some connectivity to the brain may remain and be restorable.
For paralyzed patients, this is probably the most hopeful finding of all.
“It’s a whole new ball game in how we think about the spinal cord,” he said.
The findings have stirred so much interest that offshore clinics have already sprung up offering to cure paralysis for hefty fees using a combination of electrical stimulation and stem cell injections. Such treatments are not FDA approved and could prove harmful, prompting the Reeve Foundation to issue a warning distancing the research it supports from such clinics.
A paralyzed athlete works out again
After an accident left him paralyzed, Irish endurance athlete Mark Pollock thought his days of tough workouts were over.
Then he met Edgerton.
The stimulation technique gave him enough control over his legs that Pollock was able to actively work out, with the help of a computerized robotic exoskeleton — a sort of backpack with leg braces.
“It’s addictive. It feels different immediately,” said Pollock, 40, who has been able to increase his heart rate to 166. “To feel your heart working, that feedback loop, it’s really motivating.”
Many clinicians are intrigued, but remain cautious.
Dr. Steven Vanni, a neurosurgeon at the University of Miami Spine Institute, sees great potential but doubts the technique would help people who are completely paralyzed walk without external devices to help them. He said he hoped to see the therapy verified in large, multi-center trials.
To organize and fund such trials, Edgerton has founded a company, NeuroRecovery Technologies, Inc. With federal funding, he’s also continuing research: tests of patients with paralyzed upper limbs, the first female patient, and, of course, more animal studies.
Edgerton is both humbled and bemused that so many people call his work a breakthrough — given that he’s been working on it for four decades. To him, it’s just another step that builds on the work of dozens of scientists in his lab and others around the world.
Not the retiring type — he says he’ll likely “crash in the saddle” — Edgerton has set a new goal of getting his patients to walk, not just control their limbs. He’s now working with machine learning experts to create and test new devices that provide the more complex and flexible spinal stimulation that walking requires.
“Today’s technology is equivalent to the Model T Ford,” he said. “I know we can do better.”
By Usha Lee McFarling
