An incomplete grasp of how the G4C2 repeat expansion in C9orf72 leads to amyotrophic lateral sclerosis and frontotemporal dementia has hindered progress in treatment development. Now, a study has combined unbiased genetic screens and CRISPR–Cas9 gene editing to validate known molecular pathways and identify novel therapeutic targets involved in G4C2 repeat pathogenesis.
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Acknowledgements
This work was supported by the Canadian Institute of Health Research (S.P.); National Institutes of Health/National Institute of Neurological Disorders and Stroke (R35NS097273 (L.P.); P01NS084974 (L.P.); P01NS099114 (L.P.); R01NS088689 (L.P.); R35NS097263 (L.P.); R21NS084528 (L.P.)); National Institute of Environmental Health Services (R01ES20395 (L.P.)); Department of Defense (ALSRP AL130125 (L.P.)); Mayo Clinic Foundation (L.P.); Amyotrophic Lateral Sclerosis Association (L.P.), Robert Packard Center for ALS Research at Johns Hopkins (L.P.), and Target ALS (L.P.). We would like to thank C. Cook, T. Gendron and Y.-J. Zhang for their thoughtful critiques.
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Pickles, S., Petrucelli, L. CRISPR expands insight into the mechanisms of ALS and FTD. Nat Rev Neurol 14, 321–323 (2018). https://doi.org/10.1038/s41582-018-0005-z
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DOI: https://doi.org/10.1038/s41582-018-0005-z
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