Combining multi-omics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy

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 lifespan, weight and key molecular networks in skeletal muscle. 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