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21 - 11 - 2016

Paralyzed primates walk again: 5 questions to Erwan Bézard, co-author of the study

Erwan Bézard, co-author of the work that led to paralyzed monkeys walking again and researcher at the Institute of Neurodegenerative Diseases (IND) at the University of Bordeaux, tells us more about this breakthrough for paralyzed people. 

Paralyzed primates walk again: 5 questions to Erwan Bézard, co-author of the study
 Published on November 9th in Nature, a scientific study in macaques announced a major breakthrough in the field of paralysis. An international scientific consortium le by Gregoire Courtine (EPFL) managed to make macaques with spinal cord injuries walk again using a brain-spinal cord interface. Erwan Bézard, co-author of the study and head of the Institute of Neurodegenerative Diseases of the University of Bordeaux (CNRS, UMR 5293) agreed to answer our questions to learn more about this innovative work.   What were the major steps that led to this success ? What role did you play ?  E.B.: “In all, this research took 7 years and involved many actors because it used many different techniques. Grégoire Courtine of the University of Lausanne coordinated and imbricated the different parts of this work. For my part, I supervised the experiments in macaques. They were conducted in my laboratory in China, not Bordeaux, because we had too many animals and it exceeded the laboratory’s capacity. The European project lasted 5 years, from 2010 to 2015, and required a lot of work in the animal upstream, before injury and tests. We first needed to develop tools and adapt the device we used in primates (it had already been tested in rats before, Ed.). Then we went on to do quite standard scientific experiments with trial and error to improve the algorithms that decode the cortical activity of the macaques, and the assembly of a wireless platform allowing the analysis of the primates’ movements. The different tools were then combined to be used in a healthy animal, then in the injured animal. In June 2015, the first monkeys were given implants.”   Is the rhesus macaque the ideal model for this type of research ? Would research in rodents not have been enough ?  E.B. : “It is a very good model – the ideal model I’m not sure – but in any case, it is the ideal model on which to experiment. Grégoire Courtine and almost the entire scientific community working on spinal cord injuries use rodents, which causes some problems. Indeed, rodents are mainly spinal animals: their movements are mainly managed at the spinal cord level, unlike humans. In rodents, the signals between the motor cortex and the spinal cord are not as necessary, motion is only very little cortical, and the motor cortex is less developed than in primates. There is no direct projection from the motor cortex to the motor neurons. Rodents are quadrupeds but with an automatic component. Conversely, motion in primates is mainly cortical, just like in humans. The control of fine motor skills and the decision of movement happen in the cortex with 4 to 5% of the projections that are directly onto motor neurons. But I have remained cautious in designating the macaque as an ideal model, exactly because it is still a quadruped animal. It is mainly bipedal, its arms are merely used for balance, but it is nevertheless a quadruped when it moves on the ground. On the other hand, humans are fully bipedal. The limitation of the study is there. The device will almost certainly work to restore an alternate left-right movement of the legs, but will humans be able to control their posture and their body weight. This still remains unknown, as it is not testable. We can only work in rhesus macaques, which is an animal raised specifically for research. I must point out that the experiments were performed in China, but since the funding is European, European regulations were followed. Therefore, we justified the importance of the research, demonstrated that the strategy is effective, and used animals raised for the specific purpose. For my part, I use at least F2 macaques, which are 2nd generations of animals bred in captivity.”  Can we one days hope to no longer need animal experiments entirely ? (computer models, stem cells, etc.) ?  E.B. : “It is a naïve vision to think that one is able to summarize the complexity of a brain into a computer model… One can model maybe dozens or hundreds of neurones, maybe up to a few thousands or millions, but not very precisely. The computational capacity of a neural network is far superior to what we are capable of modelling. Efforts are being made towards progressively moving to modelling, but between using a model to understand a mechanism at play and using a model to replace an experiment, it is a whole different world. Models are currently being used to support experiments to eliminate hypotheses that don’t need to be tested physiologically, but it cannot replace them completely.”  What is France’s position on primate experiments? Does France hold a strong hand in this area?  E.B. : “France has a special position, because animal experiments is strongly opposed in Europe, particularly primate research. Many countries preferred giving up under pressure, even though there is a scientific consensus that states that animal research is necessary. It becomes complicated in northern Europe but also in southern Europe. Very few countries do primate research in the world. Even in the United States, it is more and more difficult. France and Asia are the main ones left standing. We are in a country with real strengths. There are incredible facilities in Marseille, Paris, Lille, Lyon etc. We have a real capacity, a real knowledge and specialized researchers in primate research. I think that France has indeed a strong hand from the point of view of science geopolitics. I do a lot of mainstream conferences, and I never have aggressive questions. There can be, of course, concerns and questions, but on the hole, there is no real revocation of the need for these experiments, as long as they are controlled and regulated (notably by the 3R rule, Ed.). We are a unique case in Europe, and for French research, it is important to step up to the international level in this field.”  What are the next steps, areas for improvement, remaining grey areas concerning this neurotechnology? When should we expect it to be used in humans ? E.B.: “Now, the system only needs improving. We need to improve the lifespan of the implant and its signal quality on the long run. We also need to develop a “downgraded” version of the device in terms of informative content, ie replace the web of electrodes currently placed in the brain via a comb by surface electrodes. It involved using local field potentials, both to facilitate implantation for neurosurgeons and to guarantee the durability of the device. This is a lot of work but it has already begun. Moreover, this technique treats the symptoms but not the spinal lesion itself. A curative approach is a parallel approach to this symptomatic treatment, and tries to reconstruct the spinal cord, using stem cells, pharmaceutical cocktails etc. The two approaches are complementary. As for the application of the device in humans, the first clinical trials have already begun, and in all, 8 patients will be given the device in the next two years. So we can imagine that this technique could be used at a larger scale in several countries within the next 5 to 6 years. For now, we are in a phase 1-2 in paralyzed patients, to see if there is a potential therapeutic effect.” Interviewed by Hélène Bour