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Therapeutic strategies for MND are designed to confer neuroprotection, using trophic factors, anti\u2010apoptotic proteins, as well as antioxidants and anti\u2010excitotoxicity agents. Although a large number of therapeutic clinical trials have been attempted, none has been shown satisfactory for MND at this time. A variety of strategies have emerged for motor neuron gene transfer. Application of these approaches has yielded therapeutic results in cell culture and animal models, including the <jats:italic>SOD1<\/jats:italic> models of ALS. In this study we describe the gene\u2010based treatment of MND in general, examining the potential viral vector candidates, gene delivery strategies, and main therapeutic approaches currently attempted. Finally, we discuss future directions and potential strategies for more effective motor neuron gene delivery and clinical translation. 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