When he was 36 years old, Marc Gauthier, a citizen of Bordeaux (France) began to have problems with movement and coordination, tremors and stiffness. He was diagnosed with very early Parkinson’s. At the beginning of the century, he received a double brain implant. On the one hand, they installed a dopamine generator, a key neurotransmitter in the organization of movement, and at the same time a deep brain stimulator (DBS) in the basal ganglia, the part of the brain that should produce dopamine naturally. But, after improvement, the falls returned and even worsened, as well as the inability to get up or the continuous blocking while he walked. Situations as everyday as climbing stairs were an ordeal; After a few trembling first steps, he ended up turning around. However, last Sunday he went to have coffee with Eduardo Martín Moraud, a Spanish scientist who is part of the team that implanted a new neuroprosthesis two years ago. “He walked normally and had no problems even getting on the subway,” says Martín. In Gauthier’s own words, “I’m not even afraid of stairs anymore.”
Martín has been working with Grégoire Courtine, professor at the Federal Polytechnic School of Lausanne (Switzerland) since he directed his doctorate. Together with Courtine and neurosurgeon Jocelyne Bloch, from the university hospital in the same city, they have been researching for years how to help paraplegics walk again. In this long-distance race, they first investigated it with rats. After working the closest thing to a miracle, they tested their way of bypassing spinal injuries that short-circuited communication between legs and brain in monkeys. Validated in an animal model, they began testing it in humans with positive results in 2018. Last year they managed to enable three paraplegic people to recover their ability to walk the day after the operation after installing a set of electrodes in their lower back. “Already in the scholarship that Courtine applied for in 2009, it mentioned that this system could also be applied to people who had Parkinson’s,” recalls Martín. And that is what they have done with Gauthier.
The results of the work of this team, made up of fifteen neuroscientists, neurosurgeons, doctors, nurses or rehabilitators, have just been published in the scientific journal Nature Medicine. After years of research with paraplegics, it may seem strange that they recruited a Parkinson’s patient like Gauthier. In principle, a neurodegenerative disease that occurs deep in the brain does not have much to do with paraplegia caused because an accident has destroyed a young person’s spinal cord. “Regardless of the origin of the problem, all control of the legs passes through the spinal cord. In one case, information does not reach the brain because it is sectioned, in the other the information does go down, but it is anomalous,” explains Martín.
In the lower back area, in the spinal portion of the lumbar and sacral regions of the spine, there is a set of motor neurons that are responsible for ordering the leg muscles to activate. They are also the ones that receive information from the legs about their state, whether movement or rest, and which they send up the spinal cord. That is where they have acted now, somewhat forgetting about Parkinson’s. In this kind of deception of the brain, epidural stimulation has achieved something like correcting the erroneous information that came from the cerebral motor cortex.
“I’m not even afraid of stairs anymore.”
Marc Gauthier, sick with Parkinson’s for 25 years
When Gauthier arrived at the headquarters of NeuroRestore, the center where Martín works and of which both Courtine and Bloch are co-directors, two years ago, his locomotor system had serious problems. Many of the times he intended to get up from the chair, his legs would not respond. When he managed it he fell five or six times a day and he was unable to walk a few meters without being forced to stop as if frozen. In the videos that scientists have distributed there are two scenes that make the heart shrink. In one, a caregiver helps a trembling Gauthier climb some stairs. When he barely had three or four, he stops and has to turn around and give up. Another seems comical, if it were not for the unfortunate nature of the situation. With short, fearful steps, the Bordeaux man reaches the door of an elevator. He waits for him to open and when he does, he is unable to enter, is locked, and the door closes again. Like this several times.
After the implant, the patient spent six months in Switzerland, testing how he and the entire system fit together in an intensive rehabilitation program. He had to recover things that began to be lost a quarter of a century ago. Since he returned to Bordeaux, he has gone on trips on several occasions, he is able to do five kilometer walks without major problems and, as he told Martín last Sunday, he felt very good and had lost many fears. In the second batch of videos (see above) after the implant and training, he manages to get up from the chair, go up the stairs by himself and get into an elevator.
“It is impressive to see how selectively electrically stimulating the spinal cord,” explains Bloch, the neurosurgeon who performed the implant on Gauthier. “Just as we had done with paraplegic patients, we can correct the gait disorders caused by Parkinson’s disease.” Every six months he returns to Switzerland for a check-up. The Frenchman uses the neuroprosthesis more than eight hours a day. He only turns it off when he plans to sit for a while or when he goes to sleep and turns it on when he wakes up.
To get to Gauthier’s happy ending, scientists first had to refine their idea. They had a lot of accumulated knowledge from more than a decade researching paraplegics. But Parkinson’s is very different. They had to learn which area to stimulate with the electrodes, with what intensity, see what was happening in the motor cortex to find between muscle movement and brain activation. They were not starting from scratch, but there were many unknowns to clear up. What they did was first test the system with nine rhesus macaques to whom they administered a compound to induce a disorder with symptoms like those of Parkinson’s, then studying the kinetics of the animals and comparing it with that of 25 people with Parkinson’s and nine healthy people. With that information, they then implanted the electrode arrays in four of the monkeys and began modulating the signal, measuring the limb response and its correlate in brain activity. They verified that the system decoded brain instructions well. Then came Gauthier’s turn.
“There is only one participant and we do not know if all individuals with Parkinson’s disease will respond to the therapy”
Grégoire Courtine, professor at the Federal Polytechnic School of Lausanne
The Frenchman has already returned to Bordeaux, with his implant. The set of electrodes is one of those used to mitigate chronic pain in certain segments of patients. Now, a Swiss company, ONWARD Medical, is designing specific ones to place for Parkinson’s patients. In parallel, Courtine’s team has received a grant of one million dollars (about 930,000 euros) from the Michael J. Fox Foundation for Parkinson’s Research for the next phase of the project: implanting six other people. In an interview distributed by her University, Courtine recalls: “He is only one participant and we do not know if all individuals with Parkinson’s disease will respond to therapy. But we are committed to developing technology with the true purpose of [lograr] medical advances adapted to this disease.”
As Martín, the Spanish scientist, remembers, Parkinson’s is very evil: “It is a very variable disease, which changes over time in the same patient and develops differently in different people.” In fact, it is so heterogeneous that while some do not develop motor problems until a very advanced stage, others see their gait altered from the beginning. Hence the need to test the implant on as many people as possible. In January they will begin to select the six candidates for their second phase. If it goes well, there will be a third, “we trust that in several hospitals and countries,” the Spaniard concludes, before giving hope to the thousands of people affected by Parkinson’s disease with the large-scale manufacturing of this device.
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