This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Multiple factors are responsible for disease causation in amyotrophic lateral sclerosis (ALS or Lou Gehrig s disease). Excess free radicals, energy mishandling, excitotoxicity, activation of cell death pathways and inflammation likely all contribute to disease causation and progression in ALS. Past clinical trials may have been negative in part because they tested single agents, usually influencing only one mechanism of cell death. Combinations of agents that affect different and multiple mechanisms of neurodegeneration may be necessary to reach meaningful outcomes in trials of ALS. This trial attempts two novel concepts in ALS: 1) a novel study design aimed at faster screening of medications that are effective; and 2) novel combination of drugs targeting different aspects of disease.
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