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The spinal cord appears especially vulnerable in CLN1 disease, a fatal inherited lysosomal storage disorder. Our data reveal a much earlier onset of spinal cord disease and accompanying behavioural changes in CLN1 mice, while spinal maturation is still ongoing. Our multi‐disciplinary data provide new insights into the spatio‐temporal staging of CLN1 pathogenesis during ongoing postnatal maturation, and highlight the need to deliver therapies during the presymptomatic period.

Spinal manifestations of CLN1 disease start during the early postnatal period