Lithium therapy is able to reduce oxidative stress in amyotrophic lateral sclerosis patients

Objectives: The causes of motorneurons loss in Amyotrophic Lateral Sclerosis (ALS) are still unknown, but accumulating evidences indicate that oxidative stress is involved in the pathogenesis of this disease. Recently, a possible role of lithium salts on ALS treatment has been proposed. Lithium, a mood-stabilizing drug, is increasingly recognized as neuroprotectant, mainly for mechanisms linked to autophagy. Methods: We tested, in an open label therapeutic trial, the effect of lithium, at targeted plasma levels ranging from 0.4 to 0.8 mEq/liter, on clinical and oxidative stress-related laboratory parameters in 30 ALS patients. In the enrolled patients, we assessed blood levels of advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP), total glutathione, as well as disease-related ALSFRS-r andMRC scales at baseline and at 6 months after the targeted plasma lithium level was achieved. Results: Reduction ofAOPP (p=0.005) and increase of total glutathione (p=0.002), as compared to the values before treatment, were observed. FRAP increased but not significantly. Clinical evaluations at 6 months after the targeted plasma lithium level was achieved, showed a decrease of ALS-FRS and MRC scale scores compared to pre-treatment’s one, but not significantly. Conclusion: Lithium therapy is able to reduce circulating levels of blood oxidative stress markers inALS.Whether or not the modification of oxidative stress markers and antioxidant defence is related to a direct effect of this drug on pathogenic mechanism of the disease is still an open question, to be addressed with long term studies.