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Combining multiomics 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 potentially novel treatments to alleviate muscle pathology combining transcriptomics, proteomics,...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410072/ https://www.ncbi.nlm.nih.gov/pubmed/34236053 http://dx.doi.org/10.1172/jci.insight.149446 |
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author | 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 J.A. Webber, Caleb Bowerman, Melissa |
author_facet | 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 J.A. Webber, Caleb Bowerman, Melissa |
author_sort | Meijboom, Katharina E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8410072 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-84100722021-09-07 Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy 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 J.A. Webber, Caleb Bowerman, Melissa JCI Insight Research Article 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. American Society for Clinical Investigation 2021-07-08 /pmc/articles/PMC8410072/ /pubmed/34236053 http://dx.doi.org/10.1172/jci.insight.149446 Text en © 2021 Meijboom et al. https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article 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 J.A. Webber, Caleb Bowerman, Melissa Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy |
title | Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy |
title_full | Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy |
title_fullStr | Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy |
title_full_unstemmed | Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy |
title_short | Combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy |
title_sort | combining multiomics and drug perturbation profiles to identify muscle-specific treatments for spinal muscular atrophy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410072/ https://www.ncbi.nlm.nih.gov/pubmed/34236053 http://dx.doi.org/10.1172/jci.insight.149446 |
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