Amyotrophic Lateral Sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the destruction of the motor neurons. It usually affects people between 40 and 60-year-old and the average survival from onset to death is 3-4 years. Despite the severity of the disease and the high health care and social costs, no cure or viable long-term effective treatment has been identified. Moreover, the failure to translate positive preclinical results from the SOD1 mouse model into

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... cal efficacy has raised questions about the translational suitability of this model. For this reason, the TDP-43 transgenic mouse model was created by overexpressing the mutant human TDP-43 gene, mutation directly related with ALS. In this study we characterized this mouse strain TDP-43, recognized as a preclinical mouse model for ALS disorder. We observed neuromuscular disorders, peripheral nerve electrophysiological impairment and histological anomalies at 3 months old. We also demonstrated that intrathecal injection of AAV1 expressing shRNA for casein kinase-1δ (CK1δ) attenuated the peripheral degenerative phenotype in this ALS model. Our data confirm that TDP-43 mouse strain is a robust and reproducible model to analyze the neuropathy disorders of ALS and that gene therapy silencing CK1δ is a promising therapy for human ALS disorder, and can be used as a positive reference control for additional new drugs efficacy studies targeting ALS.