There are four main hypotheses about the cause of ALS: excitotoxicity linked to 
glutamate receptor overactivation; mutation of the superoxide dismutase gene; 
production of autoantibodies to calcium channels; neurofilament accumulation. 
The motoneuron degeneration characteristic of ALS could be caused by any one or 
a combination of these mechanisms. Future therapeutic approaches should be based 
on these mechanisms and given in combination so that different levels of the 
degenerative process are targeted. Protection against excitotoxicity could be 
achieved with a combination of pharmacologic agents having neuroprotective 
activity, such as antiglutamate agents (e.g., riluzole), N-methyl-D-aspartate 
(NMDA) and non-NMDA antagonists, free-radical scavengers, calcium-channel 
blockers, and neurotrophic factors. Gene transfer is a possible future approach 
when causative mutations are identified. Transfer of genes encoding 
neuroprotective agents or genetically modified cells stably expressing these 
agents is another possible strategy.