2023-05-19 09:30:24
A CEA team has developed an implant to slow the progression of Parkinson’s disease. Thanks to light, it makes it possible to keep “alive” the dopaminergic neurons of the black substances whose loss causes the symptoms of Parkinson’s.
More than 8 million people have Parkinson’s disease worldwide. And this number is increasing every year. In 2020, according to Santé Publique France, 26,000 new cases were diagnosed in France. Today, only the symptoms are treated. In other words, the disease continues to progress in those affected until they gradually lose their motor functions.
To slow down the progression of the disease, a CEA team has developed an implant which consists of illuminating neurons in order to slow their degeneration. A clinical trial, conducted with Professor Stephan Chabardès from Grenoble University Hospital, is underway. The project is supported by several funders, including the Clinatec Endowment Fund and Boston Scientific. To understand how it works and the expected results, we interviewed Cécile Moro, research director at the CEA and head of the NIR project, for “near infra-red”, for the treatment of Parkinson’s disease.
Engineering techniques: Where did you get the idea of treating Parkinson’s with light?
Cecile Moro: Light interacts with biological tissues. We have known this since 1967, when researcher André Mester realized that rats operated on for cancer healed faster when he illuminated the operated area. It was the first sighting. Then, John Mitrofanis, from the University of Sydney, a specialist in photobiomodulation, became interested in these questions. This researcher is an acquaintance of Pr Alim-Louis Benabid, co-founder of Clinatec and inventor of deep brain simulation (DBS), a treatment for certain Parkinson’s patients.
They said to themselves: why not test the light in the brain? The problem: if the light is emitted outside the skull, there is such absorption by the tissues that the light cannot reach its target, located approximately in the middle of the brain. In 2010, John Mitrofanis did a first study on a parkinsonian mouse model. And in 2011, we replicated the results on other models. We wanted the neurons that degenerate in Parkinson’s disease to do so more slowly, or even stop completely. Which would be the Holy Grail…
Is this your goal?
Our goal is to slow down the loss of dopaminergic neurons in order to delay the development of the disease and its symptoms. In fact, Parkinson’s is a disease that occurs mostly in the second half of a person’s life. Parkinson’s disease, if I simplify, is a problem of loss of dopaminergic neurons that produce dopamine, a neurotransmitter of interest. When we no longer have these neurons, we no longer have dopamine and that is when the normal functioning of the brain no longer occurs correctly.
When the disease is detected, it has already been there for many years and people have already lost 60 to 70% of the neurons involved. Which means that the 30% is enough for our body to function properly. There are some annoying effects (tremors, etc.), but not blocking to continue living. But when the disease continues to evolve until the virtual disappearance of dopaminergic neurons, there are motor symptoms that make it difficult for people to work. It is also very heavy for those around them, because those affected need a lot of help. If we slow down this disease, we can imagine people reaching the end of life with moderate motor symptoms. And therefore continue their life in better conditions.
And so you do that with an implant that sends light… can you tell us more?
Yes, it’s a device made up of three parts: a battery/simulator, an optical module that converts electrical energy into light, and an optical fiber that goes down inside the brain, near the black substances that are brain regions where dopaminergic neurons die in Parkinson’s disease. The CEA carried out all the integration of the three technological bricks to obtain a functional and qualified object.
It is an invasive technology, but requires a moderately invasive intervention for a neurosurgeon. The battery/simulator part is located under the collarbone. The cables are also passed under the skin. A trepanation is performed to replace the bone with the optical box, from which emerges an optical fiber introduced into the brain. The optical fiber will mainly descend into the ventricles of the brain, without damaging any tissue. We arrive at a few millimeters from the area to be protected. We’re in a natural corridor, so it’s a lot less invasive than going through just brain tissue.
And so the light maintains the neurons?
The mechanism of action is not completely known, far from it. What we do know is that light stimulates mitochondria, small organelles in cells that provide energy. The energy molecule of cells is called ATP. And light boosts the functioning of cytochrome C oxidase, a set of proteins located in the mitochondria that manufactures ATP. There are probably other mechanisms at play, but we don’t know them yet. Teams are working on it. It is believed that by providing energy to the cells, they are more resistant to stress, therefore dying less. And as they die less, the disease progresses more slowly.
Are you the only ones in the world working on this?
There are several teams around the world working on photobiomodulation, the effect of light on tissue. However, to our knowledge, we are the only ones to do so using an implanted device.
You have an ongoing clinical trial, what are the objectives?
The clinical trial started in 2021. To date, we have three patients implanted out of the seven at term. The objective of the clinical trial is to verify the feasibility and safety of this therapeutic approach. But we will also have a first evaluation of the effectiveness of our “light treatment” approach. We follow our patients for four years to see how the disease evolves and in particular the dopaminergic neurons. We are able by imaging techniques to quantify them, to watch how these neurons evolve.
The first patient has two years of hindsight to date and so far it is going well. We are not committing to the therapeutic results, but from a feasibility point of view, we are getting there very well and the patient has not had any side effects for the moment. We will have the result of the entire clinical trial four years after the implantation of the last patient, around 2028. If the results are good and there is indeed protection of the neurons concerned, it would be desirable to go to a larger trial. And in 10 or 15 years, we can hope that the device will be available to patients.
Before the creation of the implant, what were the steps?
We did simulations to see how light propagates, how it is absorbed by the different structures of the brain to get an estimate of the dose of light received for model Parkinsonian tissues. We carried out technical tests of the functioning of the implant (for example by checking that there is no heating at the level of the illuminated tissues), as well as regulatory tests.
In terms of operation, is it programmed or remotely controlled?
The implant is controlled by the stimulator. We choose the illumination profile when we connect to the implant via an adequate antenna during surgery and at each control visit. Then, the patient must regularly recharge his battery, with an induction charger at the level of the clavicle.
Do you do different tests for different patients?
We know what we want to send in terms of light and frequency. At each patient visit, we question the patient’s box and we are able to see how the box has worked over the past months: is the illumination done well, is the quantity good, how patient has recharged, etc. Because if it does not recharge for example, there is no treatment. And when our patients come on site, we carry out more specific tests to ensure that the implant is working well.
And to see if it works on the neurons?
We do neurological tests, to assess the disease. We are adding finer gait and mobility tests for the hands and feet. This gives us the symptoms, but not the slowing down of the disease. To see if the disease is slowing down, they are given a PET-SCAN, dopaminergic imaging, once a year.
To be able to advance in your research and achieve this implant, you have received funding…
Yes, and it is very important for disruptive and pioneering projects to have funders who trust us in order to seek other funds afterwards. Because 12 years ago, in the beginning, few people believed in it! We were fortunate to be supported by the CEA and other funding. Thanks to this, we were able to carry out a proof of concept which enabled us to seek other funds from foundations and patrons. Then an industrialist, seeing our advanced results, dared to believe it.
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