New Deep Brain Stimulation Target Shows Promise for Restoring Walking
University of Miami Miller School of Medicine researchers are testing a novel deep brain stimulation approach that improves walking in Parkinson’s disease and could help people with incomplete spinal cord injuries.
Two very different neurological conditions — Parkinson’s disease and incomplete spinal cord injuries — can interfere with the simple act of walking. Researchers at the University of Miami’s Miller School of Medicine are developing a single approach to address both by stimulating a brain area that initiates this movement.
Their strategy adapts deep brain stimulation (DBS), a well-established treatment for Parkinson’s disease, by targeting a different region of the brain than the conventional form of this therapy. Brian Noga, Ph.D., a research professor of neurological surgery at the Miller School’s Miami Project to Cure Paralysis, identified this target through years of pre-clinical research into the control of walking. Dr. Noga found that stimulating a cluster of cells deep in the brainstem could produce walking “within seconds, if not instantaneously.”
Dr. Noga recently collaborated with neurosurgeon Jonathan Jagid, M.D., a Miller School professor of clinical neurological surgery, and neurologist Corneliu Luca, M.D., Ph.D., a professor in the Movement Disorders Division, on a pilot study in Parkinson’s disease. All four participants showed improved mobility after treatment, walking longer distances faster.
“We were able to show that by utilizing standard of care for Parkinson’s disease, albeit in a different area of the brain, we could produce a consistent, positive effect,” said Dr. Jagid. “I think this is a perfect example of translating a discovery in the lab to the clinical side.”
Now the team is advancing on both fronts. They are participating in a larger, multisite Parkinson’s trial funded by the Michael J. Fox Foundation, and, in parallel, launching the first clinical trial of their approach in spinal cord injury.
Targeting the Brain’s Walking Control Center
Dr. Noga has spent his career investigating how the brain activates circuits in the spinal cord that control walking. That work led him to a part of the brainstem called the mesencephalic locomotor region (MLR). The MLR integrates signals, like the intention to walk, from higher brain areas and then routes the resulting instructions to the spinal cord. Within the MLR, he focused on the cuneiform nucleus, a cluster of cells that initiate walking.
Most spinal cord injuries are incomplete, meaning this structure’s neural pathways are not completely severed. Some communication remains between the brain and body below the injury. Dr. Noga saw an opportunity to bolster messages from the cuneiform nucleus.
“The idea is that we could improve gait by artificially enhancing the signal along these uninjured pathways,” he said.
In Parkinson’s disease, meanwhile, the loss of dopamine-producing neurons disrupts the brain’s ability to access the output pathways it needs to communicate with the spinal cord. But the result is similar. Patients struggle to walk.
This approach uses deep brain stimulation to activate a specific area of the brain that helps start and control walking. By strengthening signals from this “walking control center,” the therapy can improve stride length, speed, and coordination in people who have difficulty walking.
Early studies show benefits for people with Parkinson’s disease who struggle with walking or freezing of gait despite medication. Researchers are also testing whether this approach could help people with incomplete spinal cord injuries who still have some communication between the brain and spinal cord.
This therapy is still being studied. It has shown promising results in a small Parkinson’s disease study, and clinical trials are now underway to better understand its safety, effectiveness, and potential use for spinal cord injury.
Promising Results From a Parkinson’s Disease Pilot Trial
DBS has been used for nearly three decades to reduce Parkinson’s symptoms by introducing electrical pulses into target areas within the brain. Both DBS and medication can improve the characteristic rigidity, tremors and other movement problems. However, some of those who receive these treatments continue to struggle with gait freezing — episodes during which patients feel their feet are stuck to the ground, often while turning or walking through doorways.
“We’ve been doing pretty good for many years in improving the tremors for Parkinson’s. But what we’ve lacked is a way to improve walking for these people,” Dr. Luca said.
For the pilot trial, Dr. Jagid and his surgical team implanted directional electrodes in four Parkinson’s patients whose tremor and rigidity responded to medication but whose difficulty walking did not.
After implantation, patients returned for programming sessions during which Dr. Luca adjusted their stimulation settings. By the end of the six-month study, all four participants still needed wheelchairs, but they showed significant improvement: longer strides, faster turns and walking without freezing.
Building on these results, the team is now launching a larger Parkinson’s trial that will enroll 18 patients across the university and two other sites.
Launching the First Clinical Trial in Spinal Cord Injury
The team has also received FDA approval to test their approach in spinal cord injury patients who retain some ability to walk. Electrical stimulation is not new for this condition. Clinicians already use it to activate remaining neural connections, combining activity-based therapy with stimulation delivered externally to muscles, the spinal cord or the brain. But these methods require a specialist to set up and are not typically practical for everyday use.
By contrast, a DBS system is always available. Patients can switch stimulation on or off or make predefined adjustments with a handheld controller.
The researchers hope to see improvements comparable to those of the Parkinson’s participants, “but how those results translate to SCI remains to be seen,” Dr. Jagid said.
The team has funding from the state of Florida to recruit one patient for the trial. Dr. Noga is currently seeking funding to support as many as five more, the number the U.S. Food and Drug Administration has given the team approval to recruit.
Tags: deep brain stimulation, Department of Neurological Surgery, Dr. Brian Noga, Dr. Corneliu Luca, Dr. Jonathan Jagid, movement disorders, Movement Disorders Division, neurological surgery, Parkinson's disease, SCI, spinal cord injuries, The Miami Project to Cure Paralysis