We recently published a paper (1) showing that autophagy may be a plausible therapeutic target in amyotrophic lateral sclerosis (ALS). Lithium has known neuroprotective properties and is an inducer of autophagy. Treatment of ALS motor neurons with lithium led to the removal of altered mitochondria and the appearance of newly formed, intact, mitochondria. This effect was apparent in different experimental settings ranging from different cell lines, cultured ventral spinal cord cells bearing the G93A mutation and within motor neurons from G93A mice in vivo. Strikingly, lithium also increased the number of lamina VII neurons, which degenerate early in the disease course in animals with the G93A mutation. This effect was associated with lithium-induced neurogenesis in the spinal cord, and with concomitant suppression of glial proliferation.

The ‘uniqueness’ of the pharmacological effects observed in the spinal cord in vitro and in vivo at experimental level prompted us to test the efficacy of lithium in human patients. Therefore, we undertook a small pilot study in a group of ALS patients. We treated 16 patients with lithium and compared this cohort with 28 patients receiving only riluzole following randomization (Table I)(see supplemental data online). None of these patients was on BIPAP or PEG tubes.