Amyotrophic lateral sclerosis: an update

Amyotrophic Lateral Sclerosis (ALS) is the most common degenerative motor neuron disease in adults. It is characterized by the progressive loss of motor neurons resulting in a complex clinical manifestation and finally, death. This review presents the most recent findings about this disease. Less than 10 % of patients are familial ALS, associated to several loci of different functions. From them, more than 20 % have mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) enzyme. Neuronal inclusions and defects in protein folding are present in both forms of ALS. Aberrant accumulation of neurofilament, defects in axonal transport, neuronal oxidative imbalance and glutamate excitoxicity are some of the possible mechanisms involved in the disease pathogenesis. Riluzol, a glutamate inhibitor, is the only approved drug for ALS treatment, producing an increase of 3 months in survival. More than 30 clinic trials have been carried out to obtain new treatments for ALS, including antioxidants, glutamate inhibitors, immunomodulators and growth factors, all with failed results. Genetic therapy, interference RNA and stem cell therapy are currently in study. Probably, the right strategy to follow must be the simultaneous intervention in different molecular events to alter the disease progression.