Effects of lithium administration on oxidative stress markers in amyotrophic lateral sclerosis patients

Objectives: Amyotrophic lateral sclerosis (ALS) is a neurological disease characterized by a selective degeneration and death of upper and lower motor neurons, initiating in mid adult life and almost invariably progressing to paralysis and death over a 1–5 year time course. The causes of motorneurons loss are still unknown, but accumulating evidences indicate that oxidative stress is involved in the pathogenesis of this disease. The only treatment actually approved for this disease is Riluzole, an antiglutamatergic drug, that prolongs survival in ALS patients by about two months. Recently it has been proposed a possible role of lithium salts on the treatment of this disease. Lithium, a well known mood-stabilizing drug used for the treatment of bipolar affective disorders, at the same time is increasingly recognized as neuroprotectant agent mainly by its effects on cellular mechanisms linked to autophagy and mitochondriogenesis. Methods: We tested the effect of lithium carbonate (plasma levels ranging from 0.4 to 0.8 mEq/l) on 20 ALS patients (mean age ± SD: 64.3 years ± 7.0). In all enrolled patients, before beginning treatment, we assessed peripheral oxidative stress markers, in particularly advanced oxidation protein products (AOPP), ferric reducing ability of plasma (FRAP), total glutathione, and disease progression clinical signs quantified by ALSFRS-r and MRC scale. These evaluations were performed, during add-on to riluzole treatment, at the acquisition of the targeted plasma lithium level in plasma and at 6 months after starting lithium treatment. Results: We evidenced that, at lithium range of 0.4–0.8 mEq/l, the patients presented, compared to baseline values, significant reduction of AOPP (p\0.005), increase of FRAP but not significantly (p = 0.08) and significant increase of total glutathione (p\0.002). Conclusion: We conclude that lithium therapy is able to reduce circulating levels of blood oxidative stress markers in ALS patients. ALSFRS- r and MRC did not change after this short course treatment. Whether or not the modification of oxidative stress markers and anti-oxidant defence is related to a direct effect of this drug on pathogenicmechanism and time course of the disease is still an open question, to be addressed with long term studies in conjunction with clinical efficacy assessment.