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

• Published in: JCI insight 2021-07, Vol.6 (13)
• Main Authors: Meijboom, Katharina E, Volpato, Viola, Monzón-Sandoval, Jimena, Hoolachan, Joseph M, Hammond, Suzan M, Abendroth, Frank, de Jong, Olivier G, Hazell, Gareth, Ahlskog, Nina, Wood, Matthew Ja, Webber, Caleb, Bowerman, Melissa
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Computational Biology; Disease Models, Animal; Drug Repositioning - methods; Gene Expression Profiling - methods; Harmine - pharmacology; Humans; Mice; Muscle biology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular Atrophy, Spinal - drug therapy; Muscular Atrophy, Spinal - genetics; Muscular Atrophy, Spinal - metabolism; Neuromuscular Agents - pharmacology; Neuroscience; Proteomics - methods; Survival of Motor Neuron 1 Protein - metabolism
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.149446

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 potentially novel treatments to alleviate muscle pathology combining transcriptomics, proteomics, and perturbational data sets. 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 potentially novel treatments for use in combination with SMN restoration therapies.