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Microglial activation is thought to contribute to the progression of selective motor neuron death during amyotrophic lateral sclerosis (ALS). As minocycline has been shown to inhibit microglial activation, the therapeutic efficacy of this tetracycline derivative in the G93A mice model for familial ALS was tested. This drug with proven safety delayed disease onset and dose-dependently extended the survival of the G93A mice. At 120 days of age, minocycline protected mice from loss of motor neurons and from vacuolization. These results demonstrate that interference with immuno-inflammatory responses has a beneficial effect in the ALS mice model, suggesting this to be a potential new strategy to treat ALS.