Panel of Oxidative Stress and Inflammatory Biomarkers in ALS: A Pilot Study

Background: Pathophysiological mechanisms that contribute to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS) include oxidative stress and inflammation. We conducted a preliminary study to explore these mechanisms, to discuss their link in ALS, and to determine the feasibility of incorporating this combined analysis into current biomarkers research. Methods: We enrolled 10 ALS patients and 10 controls. We measured the activities of glutathione peroxidase, glutathione reductase, superoxyde dismutase (SOD), and the levels of serum total antioxidant status (TAS), malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG), and glutathione status (e.g. glutathione disulfide, GSSG/reduced glutathione, GSH). We analysed the concentrations of homocysteine, several cytokines, vitamins and metals by standard methods used in routine practice. Results: There was a significant decrease in TAS levels (p=0.027) and increase in 8-OHdG (p=0.014) and MDA (p=0.011) levels in ALS patients. We also observed a significantly higher GSSG/GSH ratio (p=0.022), and IL-6 (p=0.0079) and IL-8 (p=0.009) concentrations in ALS patients. Correlations were found between biological and clinical markers (homosysteine vs. clinical status at diagnosis, p=0.02) and between some biological markers such as IL-6 vs. GSSG/GSH (p=0.045) or SOD activity (p=0.017). Conclusion: We confirmed the systemic alteration of both the redox and the inflammation status in ALS patients, and we observed a link with some clinical parameters. These promising results encourage us to pursue this study with collection of combined oxidative stress and inflammatory markers. Détermination d’un panel de biomarqueurs du stress oxydant et de l’inflammation dans la SLA: une étude pilote. Contexte: Parmi les mécanismes impliqués dans la physiopathologie de la Sclérose Latérale Amyotrophique (SLA), on note un stress oxydant et des mécanismes inflammatoires. Nous avons ainsi mené une étude préliminaire afin de 1) d’explorer ces mécanismes, 2) de discuter leur lien dans la SLA, 3) de déterminer la faisabilité d’une telle analyse combinée pour une utilisation courante en recherche de biomarqueurs. Méthodes: Nous avons inclus prospectivement 10 patients SLA et 10 contrôles. Nous avons mesuré l’activité des enzymes suivantes : glutathion peroxydase, glutathion réductase, superoxyde dismutase (SOD), et les concentrations sériques des paramètres suivants : statut antioxydant total (SAT), malondialdéhyde (MDA), 8-hydroxy-2’-déo