The race of researchers to restore motor skills to paralyzed people

Giving autonomy to a paralyzed person is no longer an impossible dream. Scientists at Cambridge University recently managed to get dogs with paralyzed hind legs to walk after a spinal cord injury. The researchers used cell therapy. The treatment consisted of injecting the site of the wound, which had occurred naturally, with cells taken from the nasal cavities of the animals. The olfactory cells have the surprising characteristic of allowing the “repair” of severed nerve connections. “We are convinced that this technique could at least restore a small part of movement to people with spinal cord injuries but it is a long way before we say that they will be able to regain all the lost functions,” said the Pr Robin Franklin, one of those responsible for this research.

Paralyzed woman manages to grab a bottle and drink
To meet this challenge, other scientific teams are making different choices of cell therapy. For example, a “brain-machine interface” which consists in reconnecting the brain of a totally paralyzed person to a wheelchair, to an articulated arm, to an exoskeleton.
The technique is based on the work of deep intracerebral neurostimulation initiated by Prof. Alim-Louis Benabid at the Grenoble University Hospital at the end of the 1980s. With great care, the technology is being perfected more and more.
Already last April in the United States, Cathy, a woman paralyzed for fifteen years following a stroke, was able to rediscover a certain form of autonomy. Thanks to an external arm, robotic and controlled by his brain, this person managed to grab a bottle, bring it to his mouth and drink the coffee it contained with a straw… A human and technological feat achieved by a team from the Brain Institute in Providence (State of Rhode Island) and made possible by an electronic implant.

In France too, teams of engineers and doctors are preparing for this type of experience in humans. Clinatec, a bioclinical research center unique in the world located in Grenoble, founded in 2009, received the first green lights this summer from the regional health agency (ARS) to carry out clinical research protocols.

Listen to Prof. François Berger, neurologist and director of Clinatec: ” The striking fact is that Clinatec is labeled by the regulatory authorities and can receive patients ”.

Implants on the surface of the cortex
The team has designed two biocompatible implants that neurosurgeons can place on the surface of a person’s right and left motor cortices. “Our technique is not invasive like that of the Americans: our implants do not penetrate the cortex,” explains neurologist François Berger, director of Clinatec. These are two miniature boxes, made up of sixty electrodes, and coated with a biocompatible silicone. They pick up the electrical activity of the brain, decode it, and finally pass the command via a wireless device. “Analyzing the signal from so many electrodes was a big part of the job,” says François Berger. The algorithms have been validated by preclinical experiments on rats and then monkeys ”.

But it remains to be seen where exactly to place these implants on the surface of the human brain? “It is likely that the location of motor function in the brain of a quadriplegic person is not the same as that of a person in good physical condition,” explains Professor François Berger. This is why we are going to carry out tests to personalize the location of implants in healthy volunteers and quadriplegics, the National Agency for the Safety of Medicines and Health Products (ANSM) has given us the green light to start from here. at the end of November. ”

Listen to Prof. François Berger: ” We have implemented algorithms to personalize the location of the implants. “

Running a quadriplegic using an exoskeleton
Objective: to capture voluntary brain activity efficiently, to decode it to make it an increasingly complex command or action until it succeeds in making a quadriplegic walk using an exoskeleton. Another important step, paralyzed people, volunteers to participate in this clinical trial, will have to train to do mental tasks, to move the arm for example, a bit like high-level athletes who mentally prepare for the execution of a technical sequence or preview a race.
It will take time. Cathy, the American patient had her first implant in 2005 before she could grab a bottle seven years later. “This requires selection work to include in this trial patients capable of carrying out this training,” explains the director of Clinatec. We are working with a network of rehabilitation specialists specializing in disability, then thanks to functional imaging, neurosurgeons will be able to check the physiological state of the brain and its activity to personalize the location of the implant. Twenty people should be included in this protocol.

To make this selection and follow as closely as possible what is happening in their brain, the center has a high-performance imaging platform. “We have an operating theater equipped with the very latest medical imaging technologies in order to verify the effectiveness and harmlessness of the technology in humans,” describes François Berger. For example, the unit is equipped with an intraoperative 1.5 Tesla MRI, a first in France, which will allow very precise images of the operating field to be produced to ensure perfect identification of the implants and their impact within the tissues. “.
The specificity of Clinatec (see below) is that it concentrates medical and technological research in the same place. The design and production of the implants was done on site. Today, it welcomes teams from CEA LIST in Saclay specializing in interactive robotics to design the exoskeleton of their dreams. “But there are already working exoskeletons on the market,” says the director of Clinatec, who recalls that a Japanese company demonstrated an exoskeleton called HAL in 2011. But without direct control from a person’s brain , so there the work that there is to do is to connect the agorithm of electrical signature of the movement, resulting from the cerebral implant, to the exoskeleton to control it ”.
In other words, connecting the brain to the machine. “These are protocols that we are currently finalizing”. Subject to the necessary authorizations, testing could start by the end of 2013.

Clinatec
A French center that brings technological innovation closer to the patient’s bed

The brain machine interface project is one of the flagship projects of Clinatec, but it is not the only one far from it. For example, the bioclinical research center has developed a new medical device to explore the brain. It should allow brain cells to be captured without taking biopsies. “It is not conceivable to do a biopsy in the substantia nigra, or in the hippocampus of a person with Alzheimer’s, explains François Berger, director of Clinatec.
How to understand the molecular mechanisms involved in neurodegenerative diseases while avoiding the damage associated with a biopsy? To do this, teams of doctors, biologists and engineers have developed a very fine stylus covered with micro-nano-structured silicon, a material that has the property of capturing molecular information without damaging the tissues.

Listen to Prof. François Berger: ” We are going to make an imprint a bit like molecular biology in criminology, that is to say we are going to capture a few cells in the brain because of the properties of this material. “

The technique has been tested and validated in animals. It remains to be tested in humans. “The first application will be to explore the regions around intracerebral cancerous tumors to understand how normal tissue accepts the development of a tumor,” continues Professor Berger. As soon as we have shown in these patients that the technology is not dangerous, we will move on to pathologies which are addressed by intracerebral neurostimulation, that is to say Parkinson’s disease, movement disorders. , and why not certain psychiatric pathologies where there too the mechanisms remain little known because of the inaccessibility to the diseased brain ”.
Other projects are underway. Clinatec is preparing a trial to validate technologies capable of detecting biomarkers from the air exhaled by a person. Other teams are working on the targeted delivery of drugs … The technologies developed by Clinatec may also concern organs other than the brain, in particular in cancerology. In short, this center develops the tools of the medicine of tomorrow.

A block equipped with new technologies
It was born in 2009 from a partnership between the CHU and the University of Joseph Fournier in Grenoble, the CEA and Inserm. Since 2012, it has integrated new premises adapted to develop this synergy between doctors, biologists, engineers… An essential synergy to accelerate the transition of new technologies to the patient’s bed under the best conditions of safety. This makes it possible to speak the same language and to reinvent the protocols necessary to frame this innovative research. “What is unique in the world is that we have the entire chain on a single site for developing technologies, with a pre-clinical sector, which notably has a pet store with large animals such as pigs or monkeys, which will mimic the interventions identically to what we are going to do in humans, ”describes Professor François Berger. The center has at its disposal all the latest investigation and monitoring techniques using imaging and biology to verify efficacy and safety. “The aim is to anticipate and predict the side effects and the functioning of an innovative technology,” he underlines.

Listen to Prof. François Berger: “We placed the center where the technologies are conceived for two reasons.“

The center has six rooms to accommodate patients. The clinical sector is provided by the medical teams of the Grenoble University Hospital. Safety and ethics are the key words. “Humility too, it is important not to generate unfounded hopes or sell miracles,” says François Berger. We want to treat people who have pathologies that do not respond to conventional treatment, with two principles: benefit / risk analysis and informed consent. The center participates in ethical discussions carried out at European level on implantable medical devices and nanotechnologies.

Listen to Prof. François Berger: ” Above all, we must not generate unfounded hopes in patients, we must remain extremely humble.“