STUDY OF OLIGODENDROCYTES DEGENERATION AND STUDY OF TRANSSPINAL REPETITIVE MAGNETIC STIMULATION IN SOD1 MOUSE MODEL OF ALS

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of neurons from the motor cortex and motoneurons in the brainstem and spinal cord, leading to paralysis and death within 2–5 years of diagnosis. Current treatments are limited: riluzole modestly extends survival, and tofersen (QALSODY®) targets only patients with the SOD1 mutation. Neuronal degeneration in ALS involves both cell-autonomous processes, due to intrinsic neuronal dysfunction, and non-cell-autonomous mechanisms driven by glial cells. Astrocytes and microglia involvement are well studied. In contrast, the role of oligodendrocytes is less understood, though existing studies suggest they significantly contribute to motoneuron degeneration. This study investigates oligodendrocyte involvement in ALS pathophysiology and evaluates repetitive transspinal magnetic stimulation (rTMS) as a non-invasive therapy to improve motor function in the SOD1 mouse model. Previous work in the lab demonstrated that rTMS reduces neuronal death, demyelination, and inflammation, while promoting locomotor recovery in models of spinal cord injury. From a physiopathological standpoint, we show that disease progression is associated with a decrease in the proportion of mature oligodendrocytes and a concomitant increase in oligodendrocyte progenitor cells in the ventral horn of the lumbar spinal cord, beginning at P50. From a preclinical perspective, we further demonstrate that a 14-days rTMS treatment restores these cellular proportions to WT levels and preserves motoneuron integrity. These findings suggest that oligodendrocytes play a critical role in ALS progression and that rTMS may offer a promising therapeutic strategy to delay the onset and/or the progression of the disease.