Combining Multiomics and Drug Perturbation Profiles to Identify Muscle-specific Treatments for Spinal Muscular Atrophy

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2021 Jul 8

PMID 34236053

Citations 9

Authors

Katharina E Meijboom

Viola Volpato

Jimena Monzon-Sandoval

Joseph M Hoolachan

Suzan M Hammond

Frank Abendroth

Olivier G de Jong

Gareth Hazell

Nina Ahlskog

Matthew Ja Wood

Caleb Webber

Melissa Bowerman

Affiliations

Soon will be listed here.

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 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.

Citing Articles

Multi-omics profiling in spinal muscular atrophy (SMA): investigating lipid and metabolic alterations through longitudinal CSF analysis of Nusinersen-treated patients.

Zandl-Lang M, Zullig T, Holzer M, Eichmann T, Darnhofer B, Schwerin-Nagel A J Neurol. 2025; 272(3):183.

PMID: 39904776 PMC: 11794407. DOI: 10.1007/s00415-025-12909-4.

Spinal Muscular Atrophy: Current Medications and Re-purposed Drugs.

Basak S, Biswas N, Gill J, Ashili S Cell Mol Neurobiol. 2024; 44(1):75.

PMID: 39514016 PMC: 11549153. DOI: 10.1007/s10571-024-01511-3.

Alternative splicing of CARM1 regulated by LincGET-guided paraspeckles biases the first cell fate in mammalian early embryos.

Wang J, Zhang Y, Gao J, Feng G, Liu C, Li X Nat Struct Mol Biol. 2024; 31(9):1341-1354.

PMID: 38658621 PMC: 11402786. DOI: 10.1038/s41594-024-01292-9.

Serum myostatin as a candidate disease severity and progression biomarker of spinal muscular atrophy.

de Albuquerque A, Chadanowicz J, Giudicelli G, Staub A, Weber A, de Souza Silva J Brain Commun. 2024; 6(2):fcae062.

PMID: 38487549 PMC: 10939446. DOI: 10.1093/braincomms/fcae062.

The SMN-ribosome interplay: a new opportunity for Spinal Muscular Atrophy therapies.

Sharma G, Paganin M, Lauria F, Perenthaler E, Viero G Biochem Soc Trans. 2024; 52(1):465-479.

PMID: 38391004 PMC: 10903476. DOI: 10.1042/BST20231116.

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