Targeted antisense oligonucleotide treatment rescues developmental alterations in spinal muscular atrophy organoids.

ABSTRACT: Spinal muscular atrophy (SMA) is a severe neurological disease caused by mutations in the SMN1 gene, characterized by early onset and degeneration of lower motor neurons. Understanding early neurodevelopmental defects in SMA is crucial for optimizing therapeutic interventions. Using spinal cord and cerebral organoids generated from multiple SMA type 1 male donors, we revealed widespread disease mechanisms beyond motor neuron degeneration. Single-cell transcriptomics uncovered pervasive alterations across neural populations, from progenitors to neurons, demonstrating SMN-dependent dysregulation of neuronal differentiation programs. Multi-electrode array (MEA) analysis identified consistent hyperexcitability in both spinal and brain organoids, establishing altered electrical properties as a

SUBMITTER: Faravelli I 

PROVIDER: S-EPMC12847787 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature