Inserm Research Director
Institute of Neurodegenerative Diseases (CNRS/Université de Bordeaux)
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Unlike conventional Parkinson’s treatments, this neuroprosthesis targets the spinal cord region responsible for activating the leg muscles. © CHUV
Neuroscientists from Inserm, CNRS and Université de Bordeaux in France, along with Swiss researchers and neurosurgeons (EPFL/CHUV/UNIL), have designed and tested a “neuroprosthesis” to correct the gait disorders associated with Parkinson’s disease. In a study published in Nature Medicine, the scientists describe the development process of the device they used to treat a Parkinson’s disease patient for the first time, enabling him to walk fluidly, confidently, and without falling.
Disabling gait disorders occur in around 90% of people with advanced Parkinson’s disease and are often resistant to the treatments currently available. Developing new strategies that enable patients to walk fluidly again, avoiding the risk of falls, is therefore a priority for the research teams that have been studying this disease for many years.
This is the case of Erwan Bézard, a neuroscientist at Inserm, and his team at the Institute of Neurodegenerative Diseases (CNRS/Université de Bordeaux), who are working to understand the pathogenic mechanisms behind Parkinson’s and to develop strategies to restore motricity in various diseases. For several years, he has been working with a Swiss team led by neuroscientist Prof. Grégoire Courtine and neurosurgeon Prof. Jocelyne Bloch, who specialize in the development of spinal cord neuromodulation strategies.
In 2016, the Franco-Swiss team had already published research in Nature showing the effectiveness of a brain-spine interface – known as a “neuroprosthesis” – to restore the function of a limb paralyzed following a spinal cord injury. Its promising results had encouraged the scientists to pursue their efforts, suggesting beneficial effects in Parkinson’s disease with a similar device.
Avoiding Falls and Freezing
In this new study, the team developed a similar neuroprosthesis to compensate for falls and the phenomenon of freezing – when the feet remain glued to the ground during walking – that is sometimes associated with Parkinson’s disease.
Unlike conventional treatments for Parkinson’s, which target the brain regions directly affected by the loss of dopamine-producing neurons, this neuroprosthesis targets the spinal cord region responsible for activating the leg muscles during walking, which is not believed to be directly affected by the disease. However, the spinal cord is under the voluntary control of the motor cortex, whose activity is modified by the loss of dopaminergic neurons.
Drawing on their complementary expertise, the French and Swiss teams were able to develop and test the neuroprosthesis in a non-human primate model reproducing the locomotor deficits caused by Parkinson’s disease. The system not only reduced the locomotor deficits, but also restored walking capacity in this model by reducing freezing.
“The idea of developing a neuroprosthesis that electrically stimulates the spinal cord to harmonize gait and correct the locomotor disorders of Parkinson’s patients is the result of several years of research on the treatment of paralysis caused by spinal cord lesions”, explains Erwan Bézard, Inserm research director at the Institute of Neurodegenerative Diseases (Université de Bordeaux/CNRS).
“Previous attempts to stimulate the spinal cord have failed because they provide blanket stimulation of the locomotor centers without taking physiology into account. In our case, the stimulation overlays the natural functioning of the spinal cord neurons to target, with spatiotemporal coordination, the different muscle groups responsible for walking,” add Courtine and Bloch, co-directors of NeuroRestore, the research center based in French-speaking Switzerland.
These promising results paved the way for clinical development, to test the device in a patient.
Improvement Thanks to the Neuroprosthesis
A first patient, aged 62, who has been living with the disease for three decades, underwent surgery two years ago at Vaud University Hospital (CHUV) in Lausanne. During a precision neurosurgical procedure, Marc, originally from Bordeaux, was fitted with this new neuroprosthesis, consisting of a field of electrodes placed against the region of his spinal cord that controls gait, and an electrical-impulse generator implanted under the skin of his abdomen.
Thanks to the targeted programming of spinal-cord stimulations that adapt to his movements in real time, Marc has quickly seen his gait problems improve. After a few weeks of rehabilitation with the device, his walking has almost returned to normal.
This neuroprosthesis therefore opens up new prospects for treating the gait disorders suffered by many people with Parkinson’s disease. However, at this stage, this therapeutic concept has only demonstrated its efficacy in one person, with an implant that still has to be optimized for large-scale deployment.
The scientists are therefore working to develop a commercial version of the device that incorporates all the essential features for optimal daily use. Clinical trials on more patients are also due to start early next year.
“Our ambition is to enable widespread access to this innovative technology in order to significantly improve the quality of life of patients with Parkinson’s disease, throughout the world”, conclude the researchers.
 Thanks to a one-million-dollar donation from the Michael J. Fox Foundation for Parkinson’s research, NeuroRestore will embark on clinical trials on six new patients early next year. These trials aim not only to validate the technology developed in collaboration with ONWARD, but also to identify the patient profiles most likely to benefit from this innovative therapy. Founded by actor Michael J. Fox (Back to the Future), who himself has Parkinson’s disease, this foundation is the leading private donor in the field of Parkinson’s disease research.
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A spinal cord neuroprosthesis for locomotor deficits due to Parkinson’s disease
Nature Medicine, Novembre 2023
DOI : https://doi.org/10.1038/s41591-023-02584-1
Tomislav Milekovic 1,2,3,4,5,25, Eduardo Martin Moraud 2,3,4,25, Nicolo Macellari1,2,3,4,25, Charlotte Moerman 2,3,4,25, Flavio Raschellà1,6,25, Shiqi Sun 1,2,3,4,25, Matthew G. Perich 5,25, Camille Varescon1,2,3,4, Robin Demesmaeker 1,2,3,4,Alice Bruel7, Léa N. Bole-Feysot1,2,3,4, Giuseppe Schiavone 1,8, Elvira Pirondini2,3,9,10, Cheng YunLong11,12,13, Li Hao11,12,13, Andrea Galvez1,2,3,4, Sergio Daniel Hernandez-Charpak 1,2,3,4, Gregory Dumont1,2,3,4, Jimmy Ravier1,2,3,4, Camille G. Le Goff-Mignardot1,2,3,4, Jean-Baptiste Mignardot1,2,3,4, Gaia Carparelli1,2,3,4, Cathal Harte1,2,3,4, Nicolas Hankov1,2,3,4, Viviana Aureli1,2,3,4, Anne Watrin14, Hendrik Lambert14, David Borton 1,2,3,4,15, Jean Laurens1,16, Isabelle Vollenweider1,2,3,4, Simon Borgognon 1,2,3,4, François Bourre17,18, Michel Goillandeau17,18, Wai Kin D. Ko11,12,13, Laurent Petit 17,18, Qin Li11,12,13, Rik Buschman19, Nicholas Buse19, Maria Yaroshinsky20, Jean-Baptiste Ledoux 21, Fabio Becce 21, Mayté Castro Jimenez 22, Julien F. Bally 22, Timothy Denison23, Dominique Guehl17,18, Auke Ijspeert 7, Marco Capogrosso 1,2,3,4,9, Jordan Squair1,2,3,4, Leonie Asboth 1,2,3,4, Philip A. Starr 20, Doris D. Wang20, Stéphanie P. Lacour 1,8, Silvestro Micera 1,6,24, Chuan Qin12, Jocelyne Bloch 1,2,3,4,26 , Erwan Bezard 9,10,17,18,26 & G. Courtine 1,2,3,4,26
1 NeuroX Institute, School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL),Geneva, Switzerland.
2 Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland.
3 NeuroRestore, Defitech Center for Interventional Neurotherapies, EPFL/CHUV/UNIL, Lausanne, Switzerland.
4 Department of Neurosurgery, CHUV, Lausanne, Switzerland.
5 Department of Fundamental Neuroscience, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
6 NeuroX Institute, School of Bioengineering, EPFL, Lausanne, Switzerland.
7 Institute of Bioengineering, School of Engineering, EPFL, Lausanne, Switzerland.
8 Laboratory for Soft Bioelectronic Interfaces (LSBI), NeuroX Institute, EPFL, Lausanne, Switzerland.
9 Rehab and Neural Engineering Labs, University of Pittsburgh, Pittsburgh, PA, USA.
10 Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA.
11 Motac Neuroscience, UK-M15 6WE, Manchester, UK.
12 China Academy of Medical Sciences, Beijing, China.
13 Institute of Laboratory Animal Sciences, Manchester, UK.
14 ONWARD Medical, Lausanne, Switzerland.
15 School of Engineering, Carney Institute for Brain Science, Brown University, Providence, RI, USA.
16 Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA.
17 Universite de Bordeaux, Institut des Maladies Neurodegeneratives, UMR 5293, Bordeaux, France.
18 CNRS, Institut des Maladies Neurodegeneratives, UMR 5293, Bordeaux, France.
19 Medtronic, Minneapolis, USA.
20 Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
21 Department of Diagnostic and Interventional Radiology, CHUV/UNIL, Lausanne, Switzerland.
22 Department of Neurology, CHUV/UNIL, Lausanne, Switzerland.
23 Oxford University, Oxford, UK.
24 Department of Excellence in Robotics and AI, Biorobotics Institute, Scuola Superiore Sant’Anna, Pisa, Italy.
25 These authors contributed equally: Tomislav Milekovic, Eduardo Martin Moraud, Nicolo Macellari, Charlotte Moerman, Flavio Raschella, Shiqi Sun, Matthew G. Perich.
26 These authors jointly supervised this work: Jocelyne Bloch, Erwan Bezard, G. Courtine.