Eduardo Martín Moraud (Madrid, 39 years old) graduated in telecommunications engineering from the Polytechnic University of Madrid in 2007. In the following three decades he had time to study humanoid robotics in Kyoto and, more importantly, train and research (Japan), in artificial intelligence at the European Space Agency center in Leiden (Netherlands), with smelling robots in Paris (France) or designing a bionic hand at the University of Edinburgh (Scotland). The key to this trip was his meeting with the neuroscientist Grégoire Courtine, who was then working on spinal cord stimulation with electrodes at the Federal Polytechnic School of Zurich (Switzerland). Since then, and after his visit to the University of Oxford, Martín has found something of a calling: from the digital processing of a telecommunications signal, he led a group at the University Hospital of Lausanne (Switzerland) in which neuroprostheses are being developed. for Parkinson’s patients. His latest achievement is helping a Parkinson’s patient of 25 years walk again.
Video: EPV
Questions. How does a telecommunications engineer end up researching Parkinson’s?
Answer. After graduating, I specialized in robotics and completed my final project at a center in Japan that used humanoid robotics to understand human locomotion. It was a well-known center in Kyoto. In 1998 or 1999 they implanted a monkey and controlled the legs of a robot in Pittsburgh, USA, by reading its brain activity. It was one of the first brain-machine interfaces. After my return, I worked in France in the field of artificial intelligence. With this initially rather robotic orientation, I did the master’s project on robotic prostheses. So I had moved from telecommunications to robotics, from robotics to artificial intelligence and from there to neuroprosthetics. At that moment I saw that I was offered a job [Grègoire] Courtine. That was in 2009. It was also a neuroprosthesis, but a different neuroprosthesis, it was no longer a robot, it was electrical stimulation of the human nervous system. It seemed like a good idea to go to Zurich with him and Silvestro Micera, who supervised my thesis. I worked with rodents every other day. I had never worked with animals before. I did the entire doctoral work on rodents, which I then passed on to primates and finally to the first patient.
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Q What is electrical spinal stimulation?
R. The idea of sending electrical impulses to the nervous system has been around for 150 years. Basically, metal electrodes are placed, electrical impulses are triggered at a certain frequency, and the neurons respond to them. During the USSR period, the Russians conducted many experiments. Today it is used to treat chronic pain. If there is no response to medication, the most common therapy is to place electrodes in the spinal cord and stimulate it to prevent the signal from reaching the brain. The idea of stimulating the spinal cord for motor control hasn’t been done before, and that’s what Courtine and others have been developing for 20 years.
Q Why stimulate the spinal cord, especially the lower spine?
R. All the neurons that control the legs are located in the lumbar spinal cord. When you want to walk, the brain thinks “I’m going to walk”, the signal travels along the spinal cord and activates it, and the lumbar spinal cord coordinates the contraction of the muscles. When it splits, nothing reaches the area that is still alive. The idea is to place electrodes in this lumbar area, stimulate it with electricity, reactivate it and, in combination with physiotherapy and rehabilitation exercises, restore leg movements to a certain level after a spinal cord injury.
“The idea is to place electrodes in the lumbar area, stimulate it with electricity and reactivate it.”
Q But how is this stimulus coordinated with the intention to walk?
R. The first thing we understood may seem illogical. There are signals that go from the bone marrow to the muscle, nerves that go to the muscle, and then there are nerves that go from the muscle to the bone marrow. This is the sensory part. This means that when I stretch my arm, the muscle stretches and as it does so, the signal it sends to the spinal cord changes. The muscle tells my spinal cord, “Hey, I’m stretching.” Our stimulation works on that sensory part, not the motor part. In reality, it’s all reflex circuits, meaning that when I straighten a leg, there’s a moment where the spinal cord automatically triggers a reflex and contracts the muscle, like when you get hit in the knee. When we manage to restore a certain locomotion in patients, it is all based on reflexes, that is, we stimulate the sensory part so that when we straighten a leg, a reflex occurs and the leg moves forward.
Q And the second?
R. Second, the spinal cord has a specific anatomy. When I stimulate a high area of the lumbar spine, for example the L2 or L1 root, I activate or modulate primarily muscles that are hamstrings, whereas when I stimulate lower, on the lumbar spine, L5 or sacrum, I activate or modulate them more as extensors of the hamstrings Legs act. lower part of the leg or foot. At first we did almost no stimulation in any way. We have now positioned electrodes very precisely on the spinal cord and know exactly which electrode needs to be activated at what time.
Q And when does the brain come into play in this process?
R. The third element is the voluntary part. All of this is about what the bone marrow does and how we reactivate it. We have videos of paralyzed rats or monkeys with an electric shock to the spinal cord that appear to walk naturally but do not notice anything because it is completely involuntary. Depending on the severity of the injury, if it is minor, there will be some residual that will continue to decrease. In this case, the stimulation increases, which naturally decreases. If the injury is so severe that descent is no longer possible, you can stimulate as much as you want so that you do not reinforce a descending signal. What we did in primates, and a few months ago in a first human, was to put an implant in the brain, a second implant that decodes its activity, and we connected it to the other implant, the one for spinal cord stimulation.
Neuroengineer Eduardo Martín (left) controls the parameters of the neuroprosthesis installed by Marc Gauthier, who was diagnosed with Parkinson’s disease a quarter of a century ago. The system developed by Martín’s group has allowed him to walk again without falling or freezing. VALENTIN FLAURAUD (EFE)
Q Did they also do that with paraplegics?
R. The first was a patient in 2018 with a relatively minor injury. He was paralyzed but had some motor control that we were able to improve. The second examination involved three patients with significantly more severe injuries and no brains left. We work with them exclusively with spinal stimulation. The children trained with spinal stimulation and had a walker with buttons on the street. They pressed a button and the walking stimulus was activated. They pressed the buttons right and left, right, left.
Q But at some point he refocused his work on Parkinson’s…
R. I had a family member suffering from the disease and since I completed my PhD in 2014, my idea was to use these therapies on Parkinson’s patients. Courtine believed his approach could be applied to them. I spoke to him and to Jocelyn Bloch [neurocirujana clave en estos implantes] to advance this line. Now I’m the one leading this part of the investigation.
Q When do you think what you learned with paraplegics can be transferred to Parkinson’s?
R. Between 2017 and 2019 we conducted experiments on primates. Monkeys do not develop Parkinson’s disease, but it can be triggered with a toxin that kills dopaminergic neurons, which is the case with Parkinson’s disease. Unfortunately, you induce illness in them, but it allows you to check whether the therapeutic idea works. Then we insert implants with three goals. First you should know if it hurts. Paralyzed people don’t feel anything, but a Parkinson’s patient does. Secondly, the aim was to check whether the concept of stimulating reflexes was retained. There could be degeneration of the spinal cord that is preventing this. And third: If it doesn’t hurt and the biological basis is preserved, the reaction had to be modulated. It was time to test it on humans. We implant Marc [paciente con párkinson desde hacía 25 años] in 2021. We did the rehabilitation and he returned home. Now we stay in touch to see how it progresses or to change the configuration of the parameters, because Parkinson’s is changing. He wrote to me a few days ago: “I just ran 100 meters without falling.”
Q What can you read to spinal paraplegics and Parkinson’s patients?
R. Not long ago I gave a lecture to the Paraplegic Association of Madrid and another in Toledo [al Hospital Nacional de Parapléjicos]. We have already coordinated the expectations and pace of progress with them. Things are different for people with Parkinson’s. I don’t think they ever took that into account when they talked about these issues. I actually think it’s more complicated because we know how to assess spinal injuries. They do an MRI and an examination and know whether the person has any residual motor function. In addition, these are patients who recover after the injury until they reach a so-called plateau and no longer change significantly. This way it is easier to work. The problem with Parkinson’s patients is that we call a lot of things “Parkinson’s.” There are young and older patients with a tremor profile and people who do not tremble, with more stiffness and slower movements. Then there are those that develop in 10 years and others that take 25 years. And then there are those who experience mobility issues and those who don’t. The typical case is freezing when they remain blocked. We don’t know how to deal with it today. The neurologist knows that this man will fall, that he could break his hip, but the most he can recommend is to use a walker and be careful.
“Like any tool, it may not work for everyone, it is important to keep this in mind.”
Q And its electrodes prevent blocking…
R. What we understood with this patient is that we don’t understand everything yet. He had asymmetry, meaning he was severely affected on one side. He was very unstable and therefore fell frequently. And also a lot of freezing. We know how we improved the first two problems by stimulating the spinal cord and playing with its reflexes. We don’t know why the blockage improves, and I don’t think it’s solely due to spinal stimulation. In my opinion, when we stimulate the spinal cord, the stimulus also goes to the brain and changes something there, which improves the blockage. Nowadays Parkinson’s can be treated quite well with dopamine, and when it stops working there is deep brain stimulation, and when that doesn’t help there are duodopa pumps. What happened is that there was no tool for locomotion problems, and that’s what we’re offering now. But like any tool, it may not work for everyone. It’s important to keep this in mind. Therefore, starting in January, we expanded the investigation to include six additional people. We will look for profiles that are different from each other. In this second phase we will have electrode systems specifically designed for Parkinson’s patients.
Q How is Spanish research in this area?
R. There are very good centers with very good colleagues. Not that there is necessarily a big difference to Switzerland itself. It is true that there may not necessarily be people who work in this particular field. But in Madrid and elsewhere there are groups dedicated to Parkinson’s. This is the case with CINAC [Hospital Universitario HM Puerta del Sur], the center of José Obeso, a world-renowned neurologist. They work with so-called focused ultrasound. Like CINAC, there are others in Barcelona and Valencia that are very good. I think Spain is at the forefront here. It’s not so much about the location, but about the ability to find the environment. The reason why I am here and sometimes a little hesitant to return is because I know how difficult it is to find such a favorable environment for these kinds of jobs, especially as an engineer.
Q And the money?
R. Maybe it’s the hardest thing [en España], the founding company. Such clinical trials are very expensive. Just one implant costs 50,000 euros. We pay everything, we’re talking hundreds of thousands of euros per patient, and if the scholarships or funding they give out is, for example, 100,000 euros, then that doesn’t cover a single patient. You have to pay for the technology, the operation, the hospital stay, the physiotherapists… In Spain they give money, there are scholarships, but it depends on the level of study. There are studies that can be done with 20,000 euros, but they only gave us about a million for six patients. This aspect does limit things a bit in Spain, but I make it clear that I left in 2005, I haven’t lived there for a long time, I’m sure there are also excellent projects in Spain that I might be interested in knows nothing and who have good financing.
Q But if your system works for other patients, the economic and social benefits will be great…
R. When a patient reaches these levels of illness and loses their independence, i.e. health. The opportunity to gain years of independence, to be able to go outside and run and not fall… that helps them, it helps their families, and it helps all of us.
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