ALS-IMMUNE

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder characterized by the selective degeneration of motoneurons in the brain and spinal cord. The onset of symptoms typically occurs in adulthood, presenting as focal muscle weakness, which inevitably leads to generalized paralysis and death within 3 years. The prevalence of ALS is approximately 4-6 cases per 100000 persons annually. One of the pathological features of ALS is chronic inflammation of the central nervous system associated with immune system dysregulation. Our current knowledge of immune system involvement is mainly focused on the roles of T lymphocytes and the resident or peripheral monocyte/macrophage system. However, the complexity of neuroimmunity may be significantly underestimated, considering the variety of hematopoietic cells and their roles in inflammation and cell death. Neutrophils are the most abundant leukocytes in human blood and can initiate/maintain an inflammatory response. They also regulate adaptive immunity by suppressing T cell response. Nevertheless, the role of neutrophils in ALS remains largely unknown. The objectives of ALS-IMMUNE are to shed new light on the disease by highlighting the contribution of neutrophils to ALS pathophysiology and offering new therapeutic perspectives by targeting neutrophils. Our interdisciplinary consortium proposes to 1) Examine the transcriptional, metabolic, and lipidomic changes of ALS neutrophils to uncover novel neutrophil functions and biomarkers in affected individuals. 2) Assess the involvement of ALS neutrophils in the context of proinflammatory versus immunosuppressive T lymphocyte activities, as well as their impact on motoneuron degeneration. 3) Investigate the therapeutic possibilities of targeting neutrophils by antibody-based immunotherapy or cell therapy approaches in two distinct ALS mouse models.