Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease with an adult onset that selectively selective degenerate the upper and lower motor neurons. It results in muscle atrophy and paralysis leading to a major disability and followed by death 3 to 5 years after the onset. Most of the cases are sporadic (approximatively 90%) while 5-10% are dominantly inherited. Its pathogenesis remains unknown, and the only drug currently available, riluzole, only modestly prolongs survival. During the last 30 years, intensive genomic research unraveled up to 30 genes associated with ALS – the most frequent being SOD1, C9ORF72, FUS, TDP43 – but all the gene mutations identified are not sufficient to explain all ALS cases.

Currently, the only diagnosis and monitoring of ALS is exclusively based on clinical examination and electromyography studies, and on the exclusion of disorders mimicking ALS, such as SMA-III/IV and SBMA (spinal and bulbar muscular atrophy). In the absence of validated biomarkers, the overlapping symptoms with other diseases render ALS diagnosis often difficult, particularly early in the disease when the patient has only limited symptoms.

As several studies show that motor neuron degeneration starts at the neuromuscular junction in animal models and ALS patients and as the skeletal muscle is known to have a functional secretory activity, we hypothesized that ALS muscle cells can realize vesicles such as exosomes and participate the motor neuron death.

We hypothesise that altered exosome secretion influences the intercellular communication between the muscle and its environment, including motor neurons. This phenomenon occurs independently of muscle denervation and could be a key element in the disease progression.