Combining multi-omics and drug perutbation profiles to identify novel treatments that improve disease phenotypes in spinal muscular atrophy [RNA-seq]

We used an in-depth and parallel approach combining proteomics, transcriptomics and the drug pertubational dataset Connectivity Map (CMap) to identify differentially expressed (DE) transcripts and proteins in skeletal muscle of the severe Taiwanese Smn‍-‍/‍-‍;SMN2‍ SMA mice that could potentially be restored by known and available pharmacological compounds. This strategy uncovered several potential therapeutic candidates, including harmine, which was further evaluated in cell and animal models, showing an ability to restore molecular networks and improve several disease phenotypes, including SMN expression and lifespan. Examination of harmine treatment effect by comparison of three untreated SMA mice, three treated SMA mice, three untreated control mice and three treated control mice.