Expression profiles of skeletal muscle from Taiwanese Smn-/-;SMN2 spinal muscular atrophy mouse model treated with Pip6a-PMO

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by loss of survival motor neuron (SMN) protein. While SMN restoration therapies are beneficial, they are not a cure. We aimed to identify novel treatments to alleviate muscle pathology combining transcriptomics, proteomics and perturbational datasets. This revealed potential drug candidates for repurposing in SMA. One of the candidates, harmine, was further investigated in cell and animal models, improving multiple disease phenotypes, including SMN expression and lifespan. Our work highlights the potential of multiple and parallel data driven approaches for the development of novel treatments for use in combination with SMN restoration therapies. 18 total samples were analyzed. Smn-/-;SMN2 mice received a facial intravenous injection at postnatal day (P) 0 and P2 of Pip6a-scrambled or Pip6a-PMO (10 μg/g). The tibialis anterior was harvested from P2 untreated Smn-/-;SMN2 and WT mice, P7 untreated, Pip6a-scrambled-treated and Pip6a-PMO-treated Smn-/-;SMN2 mice and P7 untreated WT mice (3 biological replicates