Sangari S, Lackmy-Vallée A, Peyre I, Pradat PF, Marchand-Pauvert V. Afferent-driven modulation of spinal interneuron circuits across disease stages in amyotrophic lateral sclerosis. Neurobiol Dis. 2026 Feb;219:107270. doi: 10.1016/j.nbd.2026.107270.

This study uncovers a key mechanism in amyotrophic lateral sclerosis (ALS): early in the disease, spinal circuits driven by muscle spindle inputs are already disrupted. This begins with a loss of inhibition, followed by an abnormal increase in excitation.

As the disease progresses, these alterations spread beyond specific pathways, gradually affecting all spinal circuits regardless of their afferent inputs.

➡️ The result: a widespread and progressive disorganization of spinal networks, offering new insights into ALS mechanisms and paving the way for targeted therapeutic strategies.

A disrupted balance between inhibition and excitation in the spinal cord: a new key to understanding ALS.