Elevated 5 integrin expression on myeloid cells in motor areas in amyotrophic lateral sclerosis is a therapeutic target

Amyotrophic lateral sclerosis (ALS) is a fatal disease affecting upper and lower motor neurons. Microglia directly interact with motor neurons and participate in the progression of ALS. Single -cell mass cytometry (CyTOF) analysis revealed prominent expression of alpha 5 integrin in microglia and macrophages in a superoxide dismutase- 1 G93A mouse model of ALS (SOD1(G93A)). In postmortem tissues from ALS patients with various clinical ALS phenotypes and disease duration, alpha 5 integrin is prominent in motor pathways of the central and peripheral nervous system and in perivascular zones associated with the blood-brain barrier. In SOD1G93A mice, administration of a monoclonal antibody against alpha 5 integrin increased survival compared to an isotype control and improved motor function on behavioral testing. Together, these findings in mice and in humans suggest that alpha 5 integrin is a potential therapeutic target in ALS.