Journal Article

A spinal cord neuroprosthesis for locomotor deficits due to Parkinson’s disease

Raschellà, Flavio, Watrin, Anne, Wang, Doris D., Ijspeert, Auke, Lacour, Stéphanie P., Hernandez-Charpak, Sergio Daniel, Moerman, Charlotte, Capogrosso, Marco, Petit, Laurent, Galvez, Andrea, Harte, Cathal, Buschman, Rik, Borgognon, Simon, Bally, Julien F., Buse, Nicholas, Bruel, Alice, Becce, Fabio, Macellari, Nicolo, YunLong, Cheng, Aureli, Viviana, Milekovic, Tomislav, Denison, Timothy, Squair, Jordan W., Bole-Feysot, Léa N., Demesmaeker, Robin, Ko, Wai Kin D., Bloch, Jocelyne, Pirondini, Elvira, Mignardot, Jean-Baptiste, Asboth, Leonie, Schiavone, Giuseppe, Li, Qin, Yaroshinsky, Maria, Bezard, Erwan, Sun, Shiqi, Qin, Chuan, Goillandeau, Michel, Courtine, G., Bourre, François, Hankov, Nicolas, Starr, Philip A., Moraud, Eduardo Martin, Vollenweider, Isabelle, Carparelli, Gaia, Le Goff-Mignardot, Camille G., Micera, Silvestro, Ravier, Jimmy, Borton, David, Laurens, Jean, Perich, Matthew G., Lambert, Hendrik, Hao, Li, Dumont, Gregory, Jimenez, Mayté Castro, Guehl, Dominique, Ledoux, Jean-Baptiste, Varescon, Camille

2023

Overview

People with late-stage Parkinson’s disease (PD) often suffer from debilitating locomotor deficits that are resistant to currently available therapies. To alleviate these deficits, we developed a neuroprosthesis operating in closed loop that targets the dorsal root entry zones innervating lumbosacral segments to reproduce the natural spatiotemporal activation of the lumbosacral spinal cord during walking. We first developed this neuroprosthesis in a non-human primate model that replicates locomotor deficits due to PD. This neuroprosthesis not only alleviated locomotor deficits but also restored skilled walking in this model. We then implanted the neuroprosthesis in a 62-year-old male with a 30-year history of PD who presented with severe gait impairments and frequent falls that were medically refractory to currently available therapies. We found that the neuroprosthesis interacted synergistically with deep brain stimulation of the subthalamic nucleus and dopaminergic replacement therapies to alleviate asymmetry and promote longer steps, improve balance and reduce freezing of gait. This neuroprosthesis opens new perspectives to reduce the severity of locomotor deficits in people with PD. A spinal cord neuroprosthesis targeting leg motor neurons in real time improves walking and reduces freezing of gait in non-human primate models and in one individual with advanced Parkinson’s disease.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/378/2632/2634 / 692/617/375/1718 / Animal models / Animals / Biomedical and Life Sciences / Biomedicine / Cancer Research / Closed loops / Cognitive science / Deep Brain Stimulation / Dopamine receptors / Dorsal roots / Electrical stimuli / Gait / Gait - physiology / Gait Disorders, Neurologic - etiology / Gait Disorders, Neurologic - therapy / Humans / Infectious Diseases / Male / Metabolic Diseases / Molecular Medicine / Motor neurons / Movement disorders / Neural prostheses / Neurodegenerative diseases / Neurosciences / Parkinson Disease - complications / Parkinson Disease - therapy / Parkinson's disease / Primates / Prosthetics / Spinal Cord / Subthalamic nucleus / Walking