NADPH oxidase (NOX2) activity is a modifier of survival in ALS

Background: NADPH-oxidases (NOX) catalyse the formation of Reactive Oxygen Species (ROS), which play a role in the development of neurological diseases, particularly whose generated by the phagocytic isoform NOX2. Increased ROS has been observed in the Amyotrophic Lateral Sclerosis (ALS) SOD1 transgenic mouse and in this preclinical model the inactivation of NOX2 decreases ROS production and extends survival. Based on these evidences, the aim of this study has been to evaluate NOX2 activity measuring neutrophil oxidative burst in a cohort of 83 ALS patients and respective age- and gender-matched healthy controls. Methods: Oxidative burst was measured directly in fresh blood using Phagoburst™ assay by flow cytometry. Mean fluorescence intensity (MFI), emitted in response to different stimuli, leads to produce ROS and corresponds to the percentage of oxidizing cells and their enzymatic activity (GeoMean). Results: No difference was found between the mean MFI values in cases and matched controls. NOX2 activity was independent from gender and age, and in patients was not related to disease duration, site of onset (bulbar vs. spinal), or ALSFRS-R score. However, patients with a lower NOX2 activity showed a significant increase of survival. Conclusion: These findings are in keeping with the observations in the mouse model of ALS, and demonstrate the strong role of NOX2 in modifying progression in ALS patients.