Patient-specific responses to <i>SMN2</i> splice-modifying treatments in spinal muscular atrophy fibroblasts.

ABSTRACT: The availability of three therapies for the neuromuscular disease spinal muscular atrophy (SMA) highlights the need to match patients to the optimal treatment. Two of these treatments (nusinersen and risdiplam) target splicing of SMN2, but treatment outcomes vary from patient to patient. An incomplete understanding of the complex interactions among SMA genetics, SMN protein and mRNA levels, and gene-targeting treatments, limits our ability to explain this variability and identify optimal treatment strategies for individual patients. To address this, we analyzed responses to nusinersen and risdiplam in 45 primary fibroblast cell lines. Pre-treatment SMN2-FL, SMN2Δ7 mRNA, and SMN protein levels were influenced by SMN2 copy number, age, and sex. After treatment, SM

SUBMITTER: Signoria I 

PROVIDER: S-EPMC11626024 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature