The latest news and information about what's going on with SCI science and research. Brought to you by Sam Maddox, author of the Christopher & Dana Reeve Foundation Paralysis Resource Guide.

Non-Surgical Spinal Cord Stim

More cool news was released today about voluntary recovery after complete spinal cord injury. No surgery!
 
Let’s start with a statement, this from Reggie Edgerton, principal investigator behind the new publication, “Noninvasive Reactivation of Motor Descending Control after Paralysis.”
 
“People who are paralyzed are often told very early on, ‘Don’t have any hope because you’re not going to recover function below the lesion,’” he said. “They have been told that for decades, and still are today. But this was ridiculous before, and it’s even more ridiculous now.
 
 “A person can have hope, based on these results,” Edgerton said. “In my opinion, they should have hope.”
 
Spinal cord stimulation is a research story we’ve been covering for a number of years here, and as recently as last week. This is indeed a hopeful line of work, propelled by the unprecedented recovery first of Rob Summers and then the three other surgical implant epidural stim amigos in Louisville. And of course the technology makes possible The Big Idea, the Reeve clinical trial initiative to implant 36 more patients.
 
Now comes the publication in the journal Neurotrauma of results from Edgerton’s group at UCLA testing two kinds of non-surgical approaches: transcutaneous spinal cord stimulation, applied to the skin; and a prescription drug, buspirone.
 
In the new paper, five subjects, all with motor complete spinal cord injuries, were shown to improve voluntary “locomotor-like” function after the stimulation experiments. They also showed improvement – with no stimulation – after taking buspirone (Buspar) twice a day during the final four weeks of the study. This drug is often prescribed to treat anxiety by activating serotonin receptors in the brain. These same receptors are present on nerves in the spinal cord; earlier studies showed that buspirone can generate locomotion in mice with spinal cord injuries.
 
Says the new paper, funded in part by the Reeve Foundation, four-for-four is now nine-for-nine:
Herein we report the effectiveness of two novel non-invasive neuromodulatory strategies in regaining some voluntary locomotor-like leg movements after motor complete paralysis. We developed a method of electrically activating the spinal circuitry via electrodes placed on the skin overlying the lower thoracic, lumbosacral, and coccygeal vertebrae. We also demonstrate for the first time the interactive effects of administering a monoaminergic drug in combination with transcutaneous stimulation on the ability to voluntarily generate stepping-like movements of the lower limbs.
 
Using these strategies we transformed brain-spinal neuronal networks from a dormant to a functional state sufficiently to enable recovery of voluntary movement in 5/5 subjects. Pharmacological intervention combined with stimulation and training resulted in further improvement in voluntary motor control of stepping-like movements in all subjects.
 
 ... Thus, in the present and the previous studies spinal cord electrical stimulation has enabled 9/9 subjects with motor complete paralysis to move the lower limbs when they intended to do so, rather than by directly inducing a movement.
 
Edgerton, whose lab is a member of the Reeve Foundation International Research Consortium on Spinal Cord Injury, is a distinguished professor of integrative biology and physiology at UCLA and by all measures the paterfamilias for the spinal cord stimulation field; he was a co-author on the two big epidural stimulation publications that emerged from the Susan Harkema group in Louisville. Twenty years ago Harkema was Edgerton’s student.
 
UCLA researcher Yuri Gerasimenko conceived the new approach; he is also director of the laboratory of movement physiology at Russia’s Pavlov Institute. Other contributors from UCLA include neurosurgeon Daniel Lu, researchers Morteza Modaber, Roland Roy and Dimitry Sayenko, technician Sharon Zdunowski, scientist Parag Gad, laboratory coordinator Erika Morikawa and research assistant Piia Haakana. Adam Ferguson, assistant professor of neurological surgery at UC San Francisco, also contributed.
 
UCLA issued a press release today, as did the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the main federal funding source for this research.
 
From UCLA:
“Many people thought just a few years ago we might be able to achieve these results in perhaps one out of 100 subjects, but now we have nine of nine,” Edgerton said. “I think it’s a big deal, and when the subjects see their legs moving for the first time after paralysis, they say it’s a big deal.”
 
From NIBIB:
In the study, the men’s movements occurred while their legs were suspended in braces that hung from the ceiling, allowing them to move freely without resistance from gravity. Movement in this environment is not comparable to walking; nevertheless, the results signal significant progress towards the eventual goal of developing a therapy for a wide range of individuals with spinal cord injury.  
 
 “These encouraging results provide continued evidence that spinal cord injury may no longer mean a life-long sentence of paralysis and support the need for more research,” said Roderic Pettigrew, Ph.D., M.D., director of the National Institute of Biomedical Imaging and Bioengineering at NIH.  “The potential to offer a life-changing therapy to patients without requiring surgery would be a major advance; it could greatly expand the number of individuals who might benefit from spinal stimulation. It’s a wonderful example of the power that comes from combining advances in basic biological research with technological innovation.”
 
The five subjects are men from age 20 to 56, including two with thoracic injuries and three with cervical injuries. They were paralyzed for 24 to 72 months. Each underwent a series of 45 minute sessions, once a week, for approximately 18 weeks.

More from NIBIB
At the initiation of the study, the men’s legs only moved when the stimulation was strong enough to generate involuntary step-like movements. However, when the men attempted to move their legs further while receiving stimulation, their range of movement significantly increased. After just four weeks of receiving stimulation and physical training, the men were able to double their range of motion when voluntarily moving their legs while receiving stimulation. The researchers suggest that this change was due to the ability of electrical stimulation to reawaken dormant connections that may exist between the brain and the spinal cord of patients with complete motor paralysis.
 
Surprisingly, by the end of the study, and following the addition of buspirone, the men were able to move their legs with no stimulation at all and their range of movement was—on average—the same as when they were moving while receiving stimulation.

“It’s as if we’ve reawakened some networks so that once the individuals learned how to use those networks, they become less dependent and even independent of the stimulation,” said Edgerton.
 
Benefits:
Noninvasive stim won’t work for everyone but it may be a good option for those who’ve already been under the knife. “There are a lot of individuals with spinal cord injury that have already gone through many surgeries and some of them might not be up to or capable of going through another,” said Edgerton.
 
Another advantage: It won’t cost nearly as much. “The other real potentially high impact is that this intervention could be close to one-tenth the cost of the implanted stimulator.”
 
Can non-invasive stim help people bear weight, as we saw in the four epidural guys last week? They don’t know but Edgerton has already initiated a new study to try. He says he is also hoping to see if non-invasive spinal stimulation can help restore some autonomic functions, as was the case with epidural stimulation. Edgerton and his team also plan to study people with incomplete but severe paralysis. “They’re likely to improve even more,” he said.
 
Edgerton thinks both the external and internal stimulation platforms must be studied. “All patients are going to need something slightly different, and maybe non-invasive stimulation is going to be best in some cases and epidural stimulation in others,” said Edgerton. “What we need to do is maximize the clinical tool box that we have so that the physician and the patient can select a therapy that is best for them.”
 
Susan Howley, Executive VP for Research at the Reeve Foundation, echoes that view. “The Reeve Foundation has had a long and fruitful relationship with the Edgerton laboratory and we are excited about  the results of this study. We know that spinal cord injury is an enormously complex condition.  So it stands to reason that the more therapeutic options we can offer to those who live with this injury, the better their chances at recovery.”
 
The publication of Edgerton’s data on noninvasive spinal cord stimulation is especially good news for NeuroRecovery Technologies, the medical device company he helped start. NRT, based in Los Angeles, is developing both an external and internal stimulator; they hope to test products, move them though the regulatory process and on to the clinic. I asked Nick Terrafranca, CEO of NRT, for his take on the new paper:
The publication of this research should set straight the nonbelievers who doubted that a noninvasive stimulator could be used to regain voluntary movement in complete spinal cord injury patients.
 
NRT is working on two innovative stimulation platforms that represent a paradigm shift in how spinal cord injury and paralysis will be treated. We are presently focused on the noninvasive system, which we now know has tremendous potential, and also on an improved implanted stimulator, to address the well-documented shortcomings of the stimulators used in the epidural surgical experiments.
 
We are determined to move this life changing technology forward through the FDA and onto the market making it accessible to all those in need – it is our goal to have our first products on the market in two and a half years. We are optimistic that we will soon secure private funding to accelerate our efforts.
Posted by Sam Maddox on Jul 30, 2015 3:40 PM America/New_York

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