Lithium Possibly Beneficial in ALS
Low-dose lithium may slow the progression of amyotrophic lateral sclerosis (ALS), according to an Italian pilot study published in the February 12 issue of PNAS. The trial results have prompted US investigators to design a multicentered clinical trial of lithium in ALS, according to the latest issue of Neurology Today.
The Italian investigators conducted a parallel-group, randomized trial* of Carbolithium (lithium carbonate) 150 mg bid in 44 patients with nonfamilial ALS (disease duration, <5 years). All patients received Rilutek (riluzole; sanofi-aventis) 50 mg bid (the only agent that is FDA approved for the treatment of ALS). The lithium dosage for those who received the medication was adjusted by an unblinded physician to achieve a plasma level of 0.4-0.8 mEq/L (Therapeutic lithium levels in bipolar disorder have traditionally been 0.8-1.5 mEq/L).
At 15 months, all patients who received lithium (n = 16) were alive, whereas approximately 30% of patients who only received riluzole did not survive. Survival rates between the 2 groups were significantly different at 12 and 15 months. Use of lithium was also associated with the reduced progression of clinical disease, as determined by measures of physical disability and pulmonary function.
Use of lithium in ALS is based on its effects in a mouse model (also described in the study), which showed improved survival, delayed motor dysfunction, and the relative preservation of lumbar motor neurons and their associated interneurons (ie, Renshaw cells). In the mouse model, lithium reduced the motor-neuron changes that are seen in ALS (eg, accumulation of alpha-synuclein, ubiquitin, and SOD1 aggregates and vacuolization due to mitochondrial swelling) and promoted neuroprotective autophagy, which is believed to be deficient in the disease.
SOD1 = superoxide dismutase 1.
*As far as I can tell, the study was not placebo controlled.