Antisense oligonucleotides treatment uncovers differences in the modulation of dysregulated intracellular pathways in Spinal Muscular Atrophy motoneurons
Randomized trial demonstrates pathway modulation in motoneurons, implying the need for additional therapies in SMA.
Key Points
This study aims to understand how antisense oligonucleotide treatment affects intracellular pathways in motoneurons affected by spinal muscular atrophy.
Differentiated motoneurons were derived from human induced pluripotent stem cells (hiPSCs).
Nusinersen-like antisense oligonucleotides were administered to evaluate their effects on SMA motoneurons.
Apoptotic, autophagy, and protein markers were analyzed post-treatment.
ASO treatment significantly increased SMN levels and decreased apoptotic markers in SMA motoneurons.
Gemin3 protein and NF-κB members IKKβ and RelA were also increased following ASO treatment.
However, treatment did not reverse alterations in autophagy markers LC3-II and p62/SQSTM1.