Experimental models of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by the progressive loss of motor neurons, leading to profound weakness and eventual death of affected individuals. For the vast majority of patients with ALS, the etiology of the disorder is unknown, and althoug h multiple clinical trials of various therapeutic agents have been undertak en, truly effective therapy is not currently available for the disease. The selection of treatments used in ALS clinical trials frequently has its bas is in promising data obtained from experimental model systems in which the proposed agent has shown some effect in protecting motor neurons from a par ticular insult. The likelihood of a successful clinical outcome for a given treatment in ALS would therefore depend on two principal factors, includin g the similarity of the model to the disease and the biologic action of the potential therapeutic agent. Partly because early experimental models of A LS failed to replicate the disease process, treatment success in these mode ls did not carry over into human trials. Recently, however, a variety of ne wer model systems have been developed and utilized to investigate motor neu ron degeneration as related to ALS. For example, in this issue, Corse et al . use a rat spinal cord organotypic slice subjected to glutamate excitotoxi city as a model system to test the effectiveness of neurotrophic factors in preventing motor neuron degeneration. This review will assess the strength s and weaknesses of differing ALS model systems that have been used to prec linically test potential drug efficacy in ALS.