A path to better diagnose and treat Charcot disease

A path to better diagnose and treat Charcot disease

The diagnosis of amyotrophic lateral sclerosis – or Charcot disease – is difficult to pose, and is most often done by elimination, after ruling out other possible pathologies.

But a French team is highlighting a new tool that could allow better screening as well as a new treatment avenue.

Amyotrophic lateral sclerosis (ALS), better known as Charcot disease, affects 8,000 patients in France. It is a rare neurodegenerative pathology which is characterized by the destruction of the neurons responsible for motor skills, the motor neurons.

Most often occurring between the ages of 50 and 70, it leads to progressive paralysis and the death of patients in just two to five years.

Problem, as highlighted by Inserm, "lThe diagnosis of ALS is difficult to make. Indeed, the manifestations are heterogeneous at the start of the disease: weakness or cramps in an arm, a leg, swallowing or joint difficulties… Furthermore, there is no specific biomarker for the disease. Thus, the diagnosis results from the elimination of other pathologies that could lead to motor disorders, which generally takes one to two years after the onset of symptoms, thus delaying the implementation of therapeutic measures. and reduces the chances of inclusion in clinical trials at an early stage."

By testing the potential of electroencephalography, a method of brain exploration which measures the electrical activity of the brain using electrodes placed on the scalp, French researchers noted in patients affected by ALS "an imbalance between two types of waves respectively associated with the activity of excitatory and inhibitory neurons. This imbalance, in favor of greater activity of excitatory neurons to the detriment of inhibitory neurons, reflects cortical hyperexcitability."

For scientists, this phenomenon is not a surprise since it had already been described. On the other hand, the techniques to achieve this observation are difficult to implement and only work at the very beginning of the disease. Whereas electroencephalography " is very minimally invasive, very inexpensive, and can be used at different times of the disease.&amp ;quot;

"If these initial results are confirmed, electroencephalography could in the future serve as a prognostic tool for already diagnosed patients in order to evaluate, for example, the response to drug treatment, or even as a diagnostic tool. in the event of symptoms suggestive of the disease", indicate the researchers.

The hope of a cure

In addition, scientists observed a deficiency of norepinephrine in the brains of patients and mice with ALS and compared to healthy brains. To verify the role of this neuromodulator, they blocked its production in healthy animals, and showed that this causes cortical hyperexcitability, like that observed in the disease. And conversely, by administering molecules stimulating the action of norepinephrine in a mouse model of ALS, this reduced hyperexcitability and restored brain activity equivalent to that of healthy mice.

"This discovery could mark the opening of a new therapeutic avenue in ALS provided that cortical hyperexcitability is well associated to the progression of the disease ", concludes Caroline Rouaux from the Strasbourg Biomedicine Research Center. "Indeed, to date, we have observed in our study an association between the two but no causal link has yet been established. This is what we will check in the coming months."