Combining multi-omics and drug perturbation profiles to identify novel treatments that improve disease phenotypes in spinal muscular atrophy

Katharina E. Meijboom; Viola Volpato; Jimena Monzón‐Sandoval; Joseph M. Hoolachan; Suzan M. Hammond; Frank Abendroth; Olivier G. de Jong; Gareth Hazell; Nina Ahlskog; Matthew J. A. Wood; Caleb Webber; Mélissa Bowerman

doi:10.1101/2019.12.17.879353

NeurosciencebioRxivDec 17, 2019

Preprint

Combining multi-omics and drug perturbation profiles to identify novel treatments that improve disease phenotypes in spinal muscular atrophy

Katharina E. Meijboom iD, Viola Volpato iD, Jimena Monzón‐Sandoval iD, Joseph M. Hoolachan iD, Suzan M. Hammond iD, Frank Abendroth iD, Olivier G. de Jong iD, Gareth Hazell, Nina Ahlskog iD, Matthew J. A. Wood iD, Caleb Webber iD, Mélissa Bowerman iD

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Abstract

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 lead 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, parallel data driven approaches for development of novel treatments for use in combination with SMN restoration therapies.