UMMS Affiliation

Gene Therapy Center; Department of Neurology

Publication Date

2021-07-08

Document Type

Article

Disciplines

Bioinformatics | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Musculoskeletal Diseases | Nervous System Diseases | Neuroscience and Neurobiology

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.

Keywords

Bioinformatics, Drug therapy, Genetic diseases, Muscle Biology, Neuroscience

Rights and Permissions

Copyright © 2021 Meijboom et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

DOI of Published Version

10.1172/jci.insight.149446

Source

Meijboom KE, Volpato V, Monzón-Sandoval J, Hoolachan JM, Hammond SM, Abendroth F, de Jong OG, Hazell G, Ahlskog N, Wood MJ, Webber C, Bowerman M. Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy. JCI Insight. 2021 Jul 8;6(13):e149446. doi: 10.1172/jci.insight.149446. PMID: 34236053; PMCID: PMC8410072. Link to article on publisher's site

Journal/Book/Conference Title

JCI insight

Related Resources

Link to Article in PubMed

PubMed ID

34236053

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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