Recent advances in the therapy of amyotrophic lateral sclerosis: focus on excitotoxicity.

Between Charcot’s first description, in 1864, of a rapidly progressive neurodegenerative disease and the early 1990s, physicians’ efforts in the field of amyotrophic lateral sclerosis (ALS) focused mainly on the definition of the diagnostic criteria for this disease, which was for a long time considered fatal. Only recently, parallel to an improved understanding of the physiopathogenesis of the disease, have we entered the era of pharmacological treatment of ALS. In 1993, riluzole, a glutamate antagonist first approved in 1980 for the treatment of convulsions, underwent, in the USA, phase II and III trials for the treatment of ALS; it became (in 1994) the first ALS drug approved by the FDA, was registered in the USA in 1995 and is now available in over 21 countries. It is still not clear whether it slows the progression of the disease or not. Various experimental model systems, both in vivo and in vitro, have been developed to investigate the mechanisms leading to the selective motor neuron degeneration related to ALS; these models have also been used to test the efficacy of various drugs in preventing or arresting the cascade leading to degeneration. Unfort u n a t e l y, the success of the treatment in these