Targeted spinal cord stimulation with an implanted neuroprosthesis helped a Parkinson’s disease patient who had severe movement deficits walk confidently without falling, a proof-of-concept study showed.
The prosthesis targeted dorsal roots in the lumbosacral spine. It was implanted in a 62-year-old male with a 30-year history of Parkinson’s who presented with severe gait impairments and frequent falls, reported Gregoire Courtine, PhD, of École Polytechnique Fédérale de Lausanne in Switzerland, and co-authors in Nature Medicine.
Freezing of gait, a Parkinson’s symptom that had burdened the patient, nearly vanished when he used the neuroprosthesis.
Targeting dorsal roots with epidural electrical stimulation (EES) modulates the activity of neurons that control walking movements. Last year, Courtine and colleagues used EES to restore the ability to walk in a man with paralysis due to spinal cord injury.
“The idea of developing a neuroprosthetic that stimulates the spinal cord electrically to harmonize the procedure and correct locomotor disorders in patients with Parkinson’s is the result of several years of research on the treatment of paralysis due to spinal cord injuries,” Courtine said in a news briefing.
Balance and gait impairments are hallmark symptoms of Parkinson’s disease, noted Aviv Mizrahi-Kliger, MD, PhD, and Karunesh Ganguly, MD, PhD, both of the University of California San Francisco, in an editorial accompanying the research.
“They become increasingly prevalent as the disease progresses; they affect the majority of patients with late-stage Parkinson’s disease and dominate the clinical presentation at 15 years after diagnosis,” they wrote.
“The effect of freezing-of-gait is especially debilitating as these episodes manifest in a sudden and unpredictable inability to start or continue walking forward, resulting in falls and injuries,” Mizrahi-Kliger and Ganguly observed.
Levodopa, a dopamine replacement agent, addresses some Parkinson’s motor symptoms but its effect on gait and balance impairments is inconsistent, the editorialists pointed out. “Similarly, the effect of deep brain stimulation of the subthalamic nucleus on the axial symptoms of the disease is heterogeneous, which motivates the search for new avenues of therapy,” they wrote.
Courtine and colleagues developed the neuroprosthesis to restore the natural activation of leg neurons that are disrupted in people with Parkinson’s disease. They first tested it in non-human primate models. In 2021, they initiated their first trial in a man from Bordeaux with advanced Parkinson’s who had severe motor deficits, despite drug treatment and deep-brain-stimulation.
The researchers generated a personalized anatomical map of the spinal cord regions to be targeted by EES to guide the surgical implantation of the neuroprosthesis. The prosthesis was placed on the patient’s spinal cord and linked to a neurostimulator that was placed under the skin of his abdomen.
When the patient wanted to walk, he used a remote control to send signals to the stimulator to activate leg neurons. After several weeks of rehabilitation, the patient walked almost normally. Two years later, he uses his neuroprosthetic device for about 8 hours a day, turning it off when he sits for long periods or sleeps. He regularly takes walks spanning several kilometers at a time.
A key innovation of this study was its customized modulation of dorsal roots in the lumbosacral spine, Mizrahi-Kliger and Ganguly noted. “The effect in the single patient is quite impressive, but, of course, the next crucial step is to test this approach in a larger cohort of patients,” they wrote.
“It is worth pointing out that other approaches to spinal stimulation in Parkinson’s disease (for example, direct modulation of sensory columns in the spinal cord itself) can have benefits, but the effects can also be variable,” they continued.
Future studies can help determine how variable the effects of spinal EES might be, they added. Courtine and colleagues plan to carry out clinical tests on six Parkinson’s patients next year.
Funding was obtained from the Defitech Foundation, the Roger de Spoelberch Prize, ONWARD Medical, the CAMS Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, PDWALK ERANET, the Parkinson Schweiz Foundation, the European Community’s Seventh Framework Program, a Consolidator Grant from the European Research Council, the Wyss Center for Bio and Neuroengineering, the Bertarelli Foundation, and several fellowships.
Courtine and co-authors hold various patents or applications in relation to the present work. Researchers also reported relationships with ONWARD Medical, Motac Neuroscience, and Plenitudes SARL France.
Mizrahi-Kliger declared no competing interests. Ganguly has a patent for modulation of sensory inputs to improve motor recovery from stroke and has been a consultant to Cala Health.
Source Reference: Milekovic T, et al “A spinal cord neuroprosthesis for locomotor deficits due to Parkinson’s disease” Nat Med 2023; DOI: 10.1038/s41591-023-02584-1.
Source Reference: Mizrahi-Kliger A, Ganguly K “Spinal stimulation for unfreezing gait in Parkinson’s disease” Nat Med 2023; DOI: 10.1038/s41591-023-02604-0.