Daily electrical stimulation of certain nerves in the spinal cord appeared to help three people with spinal muscular atrophy (SMA), boosting leg muscle strength and allowed them to walk farther, scientists have reported.
“After some days, my legs just felt supercharged,” Doug McCullough (57) one of the participants in the month-long study at the University of Pittsburgh School of Medicine told NPR.
If the benefits of spinal stimulation are confirmed in larger trials, the approach could augment the latest drug treatments for SMA, an inherited disorder that causes muscles to waste away, wrote the researchers in Nature Medicine.
The drugs can slow or stop the disease, but don’t actually reverse its disabling symptoms.
Spinal stimulation also appears to help people with muscle weakness from a stroke. And it might eventually improve the lives of people with ALS (amyotrophic lateral sclerosis) and Parkinson’s disease, the researchers said.
Low expectation, surprising result
McCullough was 11 when he was diagnosed with a form of SMA that progresses very slowly.
SMA weakens muscles by killing off motor neurons in the spine. The first motor neurons to go are typically those controlling muscles in the shoulders, back, hips and thighs.
The most severe form of SMA causes severe symptoms in newborns. Until the first drug for SMA arrived in 2016, children typically died before the age of two.
By the time McCullough entered the Pittsburgh study, he was relying on two canes to walk, and had begun using a motorised wheelchair.
“As a person with a progressive disease, you never get any better,” he said. “You’re either maintaining, or you’re getting worse.”
So McCullough had low expectations when he arrived in Pittsburgh to have wires temporarily implanted in the part of his spine that controls leg muscles which are critical for walking.
After recovering from surgery, he went to the lab, where scientists began delivering pulses of electricity to certain nerves in his spinal cord.
At first, he felt nothing. “Then they’d start turning it up a little bit, and you would feel this faint pulse inside your body,” he said. Specifically, in his legs.
Over the course of the experiment, his legs regained some function. He could walk a few steps farther. His gait was a bit better. His legs felt stronger – even when the spinal stimulator wasn’t connected.
A much more dramatic change occurred in another participant, who was 20 and less disabled when he entered the study, said Marco Capogrosso, an assistant professor at the University of Pittsburgh and one of the study’s authors.
“He improved so much that he could walk from the family housing where they were staying for the trial, to our lab. He couldn’t do that before.”
Stimulation that lasts
Before the SMA study, researchers at the University of Pittsburgh had been using spinal stimulation to boost arm strength in people who’d had a stroke.
The treatment appeared to work by strengthening the connections among the nerve cells involved in controlling and monitoring specific arm muscles. Capogrosso and his team thought a similar approach might work on the leg muscles in people with SMA.
In both cases, the idea was to get more out of the relatively small number of nerve cells that remained intact.
But the results with SMA patients proved far greater than the researchers had anticipated, Capogrosso said.
“Friday they would come in the lab, do their tests, and then go home,” he said. “Then on Monday they would come back and suddenly they were 20% stronger.”
Much of the improvement was maintained even when the stimulator wasn’t turned on.
Capogrosso thinks that’s because stimulation had helped re-establish communication between the remaining motor neurons and other neurons involved in the circuit that allows walking.
“They had fewer motor neurons left because some of those died,” he says. “But their cells were better at controlling their muscles.”
The result supports an idea proposed in 2011 by George Mentis, a professor at Columbia University whose research focuses on spinal motor neurons.
“What people thought until that time was that if you fix the motor neurons, you will be fixing the disease,” he said.
But Mentis showed that in mice with SMA, muscle weakness appeared before motor neurons started dying.
The reason, he argued, was that SMA was also disrupting critical connections between motor neurons, which tell a muscle when to contract, and sensory neurons, which monitor what that muscle is doing.
The results in Pittsburgh suggest that spinal stimulation can restore these connections, even when the number of motor neurons has been greatly reduced, Mentis said.
If that’s true, he added, spinal stimulation could greatly improve the lives of people with SMA.
“During that month of electrical stimulation, we never reached a plateau,” he said. “They were still improving.”
So permanent spinal implants might work even better.
Spinal stimulation also might help people with other diseases that affect movement, including ALS and Parkinson’s, he suggests.
Study details
First-in-human study of epidural spinal cord stimulation in individuals with spinal muscular atrophy
Genís Prat-Ortega, Scott Ensel, Serena Donadio et al.
Published in Nature Medicine on 5 February 2025
Spinal muscular atrophy (SMA) is an inherited neurodegenerative disease causing motoneuron dysfunction, muscle weakness, fatigue and early mortality. Three new therapies can slow disease progression, enabling people to survive albeit with lingering motor impairments. Indeed, weakness and fatigue are still among patients’ main concerns. Here we show that epidural spinal cord stimulation (SCS) improved motoneuron function, thereby increasing strength, endurance and gait quality, in three adults with type 3 SMA. Preclinical works demonstrated that SMA motoneurons show low firing rates because of a loss of excitatory input from primary sensory afferents. In the present study, we hypothesised that correcting this loss with electrical stimulation of the sensory afferents could improve motoneuron function. To test this hypothesis, we implanted three adults with SMA with epidural electrodes over the lumbosacral spinal cord, targeting sensory axons of the legs. We delivered SCS for 4 weeks, 2 h per day during motor tasks. Our intervention led to improvements in strength (up to +180%), gait quality (mean step length: +40%) and endurance (mean change in 6-minute walk test: +26 m), paralleled by increased motoneuron firing rates. These changes persisted even when SCS was turned OFF. Notably, no adverse events related to the stimulation were reported.
NPR article – Spinal stimulation restored muscles wasted by rare genetic disorder (Open access)
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