People with Parkinson's disease often develop problems walking in the advanced stages. Therapies currently available are largely ineffective against walking disorders. A feasibility study with a 62-year-old patient now shows that those affected can benefit from a neuroprosthesis that specifically stimulates the spinal cord. Using wireless sensors, the prosthesis detects movement intentions. Electrodes implanted in the spinal cord then modulate the activity of the neurons responsible for these movements. In the test subject, this technique compensated for walking and balance deficits and led to an improvement in quality of life. Studies with other affected people are to follow.
Parkinson's is the second most common neurodegenerative disease in Germany after Alzheimer's. Neurons that produce the neurotransmitter dopamine die in the brainstem area. The resulting lack of dopamine leads to the typical symptoms of the disease: the ability to move and the sense of balance decrease, the muscles tremble and stiffen, and movements become smaller and slower. Around 90 percent of those affected develop walking difficulties in the advanced stages. While tremors and stiffness can usually be easily treated with dopamine replacement therapy or deep brain stimulation, walking disorders often persist despite various attempts at therapy.
Stimulation in the spinal cord
A team led by Tomislav Milekovic from the Swiss Federal Institute of Technology in Lausanne has now tested a neuroprosthesis as a potential solution in a feasibility study. “While previous therapies focused on the regions of the brain directly affected by the loss of dopamine-producing cells, our neuroprosthesis targets a region of the spinal cord that ultimately enables walking and is itself not directly affected by Parkinson’s disease,” explains Das Research team.
A technique called epidural electrical stimulation (EES) is used. The nerves in the spinal cord that control the movement of the legs are stimulated with the help of implanted electrodes. This method has already shown promise in people who are paralyzed due to spinal cord injuries. To find out whether people with Parkinson's can also benefit from this form of electrical stimulation, Milekovic and his team first carried out extensive experiments on macaques. By injecting the neurotoxin MPTP, they caused Parkinson's symptoms in the monkeys and then tested whether a neuroprosthesis could restore their movement abilities.
Neuroprosthesis alleviates walking difficulties
After the prosthesis proved successful in macaques, the researchers started a pilot test with the first human patient, a 62-year-old man who has had Parkinson's disease since he was 36 years old. Despite dopamine therapy and deep brain stimulation, he had developed a severe walking disorder that significantly affected his quality of life. “I practically couldn’t walk without falling, several times a day,” he reports. “In some situations, for example when entering an elevator, I found myself stomping on the spot as if I was frozen, so to speak.”
To find the optimal position for the electrodes, Milekovic and his team created a personalized anatomical map of the patient's relevant spinal cord regions and implanted the electrodes in such a way that they precisely target the nerve fibers that are important for walking. Wireless sensors on the patient's legs detect when they start to move and send a signal to the neuroprosthesis, which then stimulates the nerves in the spinal cord so that the patient can actually carry out the desired movement. “Non-invasive, wearable sensors are the preferred solution as long as the detection is reliable and the sensors are practical to use in everyday life,” explains the research team. However, for patients for whom such sensors are not sufficient, it would also be conceivable to derive movement intentions directly from the motor cortex with the help of additional electrodes in the brain.
Broad applicability still unclear
In the case of the 62-year-old test patient, the sensors on his legs were sufficient to reliably detect when he was attempting which movement. After a training phase lasting several weeks, he managed to develop a more stable gait with the neuroprosthesis switched on, no longer freezes while walking and hardly falls anymore. He has now been wearing the prosthesis for two years and only switches it off when he sleeps or sits for long periods of time. “It is impressive to see how we can correct the walking disorders caused by Parkinson's disease by targeted electrical stimulation of the spinal cord, as we did with paraplegics,” says Milekovic's colleague Jocelyne Bloch.
In future studies, the research team would like to test the neuroprosthesis on additional test subjects to find out which patient groups can benefit from it under which conditions. “Parkinson’s disease leads to a wide range of neurological profiles that are associated with different deficits in the musculoskeletal system,” explain the researchers. “Therefore, it remains unclear whether neuroprosthesis is effective in alleviating gait disorders, improving balance, and reducing gait freezing in all people with Parkinson's disease. Future studies therefore need to identify people who respond to this therapy.”
Source: Tomislav Milekovic (Ecole Polytechnique Fédérale de Lausanne (EPFL), Geneva) et al., Nature Medicine, doi: 10.1038/s41591-023-02584-1