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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,...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
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.
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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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