Method Profile
Neural and muscle compartments are evaluated together after SMN2 splicing-modulator treatment, linking molecular response with neuromuscular structures and contraction.
Comparison of SMN restoration, muscle maturation and integrated neuromuscular function in SMA models.
Neuromuscular organoids from three SMA type 1 patient iPSC lines and healthy pluripotent stem cell controls; detailed pharmacological analysis centers on Pt1.
Risdiplam at 250 nM or branaplam at 40 nM from day 20; day-30 transcript analysis and approximately day-60 structural/functional follow-up.
Human tissues
Spatially segregated spinal neural and skeletal muscle compartments with neuromuscular contacts.
Drug comparisons
Risdiplam, branaplam and a separate risdiplam–prednisolone comparison.
Measurements
SMN immunoblotting, single-nucleus RNA sequencing, α-bungarotoxin-associated junction measurements, myofiber diameter and live contraction analysis.
Keep molecular and functional responses separate; distinguish patient-line replication, differentiation experiments, organoids and sequenced nuclei.
Compare two splicing modulators and follow whether increased SMN/junction structures coincide with muscle growth and contraction.
Three patient lines for baseline/SMN comparisons; principal Pt1 drug structural/functional comparisons use three independent experiments with three organoids per condition.
Untreated SMA organoids, healthy controls and separate drug conditions; curare tests transmission-dependent contraction.
Both drugs increased SMN and junction-associated structures. Branaplam produced broader muscle transcriptional changes, increased myofiber diameter and stronger functional recovery in Pt1.
A neuromuscular organoid preprint compares risdiplam and branaplam across neuronal and muscle compartments. Both increased SMN protein and junction-associated structures, while branaplam produced a stronger muscle-maturation and contraction response in the principal patient model.
