Charcot disease: a new avenue of diagnosis and treatment are being studied: Femme Actuelle Le MAG

It is a disease that is still incurable: amyotrophic lateral sclerosis (ALS), which we mainly know under the name Charcot disease. This rare neurodegenerative disease results in progressive paralysis of the muscles. It is notably due to the death of certain nerve cells. Due to the absence of a disease biomarker, the diagnosis of ALS is often made by eliminating other pathologies. On average, it takes two years to make a diagnosis.

Inserm researchers looked at a tool to improve the time it takes to diagnose the disease. They discovered that electroencephalography, a test that measures and records the electrical activity of the brain, could help discover a possible therapeutic target. Their results are published in the review Science Translational Medicine.

Charcot disease: a diagnosis still difficult to make

First of all, it is important to look at the causes of Charcot disease. The latter “is due to the death of motor neurons, the nerve cells that control muscles, both in the brain (central motor neurons) and in the spinal cord (peripheral motor neurons),” as summarized by the researchers.

What makes the diagnosis difficult to make is explained in particular by the different manifestations at the start of the disease, such as “weakness or cramps in an arm, a leg, difficulty swallowing or articulating…”, all symptoms not being specific to the disease. Currently, the diagnosis is made, on average, after two years of examinations, while the different pathologies that can cause these symptoms are analyzed.

Researchers therefore wanted to reduce the diagnosis time in order to allow the implementation of therapeutic measures as quickly as possible and to increase the chances of inclusion in clinical trials at an early stage.

Measuring brain activity could help spot Charcot disease, researchers say

Initially, the researchers therefore used electroencephalography in mice suffering from the disease, a technique described by the researchers as “inexpensive” And “easy to use” Who “consists of placing electrodes on the surface of the skull to record brain activity in the form of waves”. The researchers then discovered “an imbalance between two types of waves respectively associated with the activity of excitatory neurons (stimulates neurons, editor’s note) and inhibitory neurons (which block the transmission of nervous messages, editor’s note)”.

According to the researchers, the imbalance of these two types of waves was present in all the mice tested.“The more the symptoms of the disease progress, the greater this imbalance,” researchers note. This could help detect the disease because “this atypical wave profile was detected in the animal even before the appearance of the first motor symptoms”.

Charcot disease: stimulating the production of norepinephrine, a potential therapeutic avenue under study

Subsequently, the researchers wanted to understand the origin of these modifications. To do this, experts analyzed, in sick mice, the production of neuromodulators produced by neurons to communicate with each other. They then discovered that “Norepinephrine was present in lower quantities in the brains of patients and mice with ALS and compared to healthy brains”.

To confirm their results, the researchers blocked the production of this neuromodulator in healthy animals, leading to the same imbalance as in sick mice. Conversely, after stimulating the production of norepinephrine in sick mice, they “reduced hyperexcitability and restored brain activity equivalent to that of healthy mice”.

In the press release, Caroline Rouaux, an Inserm researcher at the Biomedicine Research Center in Strasbourg, France, believes that “this discovery could mark the opening of a new therapeutic avenue in ALS provided that cortical hyperexcitability is indeed associated with disease progression”. According to her, this research work makes it possible to observe “an association between the two but no causal link has yet been established”, concludes Caroline Rouaux. New research work must therefore still be carried out.

Sources:

• Cortical hyperexcitability in mouse models and patients with amyotrophic lateral sclerosis is linked to noradrenaline deficiency – Science Translational Medicine.
• Charcot disease: a new avenue to improve the diagnosis and monitoring of patients – Inserm (press release)