Key result
TEC-1 selectively modulated SMN2 splicing over secondary targets like FOXM1 and significantly ameliorated the disease phenotype, including enhanced survival, in an SMA murine model.
Why the study?
Existing small-molecule SMN2 splicing modulators for spinal muscular atrophy modulate secondary splice targets including FOXM1, highlighting the need for selective modulators with improved tolerability.
Does the novel small molecule TEC-1 selectively modulate SMN2 splicing and improve disease phenotypes in SMA models with better tolerability than existing modulators?
Population
SMA patient-derived fibroblasts and an SMA murine model
Comparison
TEC-1 vs risdiplam, SMN-C3, or control
Design
Preclinical in vitro and in vivo study
Authors
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TEC-1 merits clinical translation studies in SMA; leaves open whether selectivity improves tolerability over existing modulators.
Does the novel small molecule TEC-1 selectively modulate SMN2 splicing and improve disease phenotypes in SMA models with better tolerability than existing modulators?
TEC-1 is a novel, CNS-penetrant SMN2 splicing modulator that improves survival and motor function in an SMA mouse model while avoiding the off-target splicing effects and genotoxicity associated with existing therapies like risdiplam.
Ando et al. (2020) studied Spinal muscular atrophy (SMA). TEC-1 vs. Vehicle, SMN-C3, risdiplam was evaluated on Survival and motor function in SMNΔ7 mice, and SMN2 splicing modulation in vitro. TEC-1 selectively modulated SMN2 splicing over secondary targets like FOXM1 and significantly ameliorated the disease phenotype, including enhanced survival, in an SMA murine model.
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