An Inserm team suggests that the characteristic symptoms of amyotrophic lateral sclerosis could actually be preceded by sleep alterations.
- Amyotrophic lateral sclerosis (SLA) leads to a degeneration of motor neurons, but a recent study suggests that sleep disorders precede the motor symptoms.
- Researchers have observed, in patients and model mice, an alteration of orexin neurons, involved in awakening. By administering an orexin inhibitor, they restored sleep and protected the snowmobiles.
- A clinical trial is underway to assess whether this approach could slow the progression of ALS. These discoveries offer a new therapeutic hope.
Amyotrophic lateral sclerosis (SLA), or Charcot’s disease, is a serious neurodegenerative disease, marked by the progressive destruction of the snowmobiles. This degeneration leads to a loss of autonomy and paralysis of the motor muscles, often fatal. If research has made it possible to better understand its genetic and biological bases, the exact mechanisms of the disease still have to decrypt.
In a new study published in the journal Science Translational Medicinea team of French scientists has just lifted the veil on the mechanisms at work in this disease a little more, suggesting that the characteristic symptoms of SLA are in fact preceded by sleep alterations.
An early link between sleep and SLA
To do this, researchers from the National Institute of Health and Medical Research (Inserm) and the University of Strasbourg, in collaboration with the German center Dzne, examined the chronology of SLA symptoms. They were interested in sleep disorders, often observed in patients due to the damage of the respiratory muscles, but which could actually appear much earlier.
By comparing sleep recordings of patients at different stages of the disease and pre-symptomatic subjects carrying genetic mutations (characteristics of SLA), the researchers found that these two groups were suffering from prolonged awakening time and ‘A reduction in deep sleep. And this, well before the appearance of motor disorders.
Restore sleep to slow down the disease?
Scientists then sought the origin of these anomalies in the brain and identified a dysfunction of orexin neurons, located in the hypothalamus and involved in the regulation of awakening. On mouse models with ALS, they found that the destruction of certain additional neurons disrupted the activity of orexin neurons.
To remedy this alteration, they administered an orexin inhibitor, already present in a sold out sleeping room. The treatment made it possible to restore the sleep of the mice and, after 15 days, to preserve their snowmobileurons. These results could thus pave the way for an unprecedented therapeutic approach.
Towards new therapeutic perspectives
A clinical trial is currently underway to assess the effectiveness of this molecule in patients with SLA. The objective is to observe whether better sleep quality can favorably influence the evolution of the disease. “Our study had the main ambition to try to reconstitute what is happening in patients before they were sick, explains Matei Bolborea, who participated in the work, in a press release. These discoveries on the chronology of symptoms allow us to rethink the role of the brain and particularly that of the hypothalamus in the beginning of the pathology and to imagine new therapeutic targets. “
Luc Dupuis, another author of the study, adds: “The discoveries of our team are important on two levels. First of all, they highlight a new chronology of SLA symptoms, again questioning the origins of the disease, and in particular the role of the brain in its genesis. They Also represent a slight hope for the patients, and those who declare the disease, imagining that Idug on the first manifestations of it can slow its extremely rapid progression. “
