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Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans

Sarcopenia, characterized by age-related loss of muscle mass, strength, and decreased physical performance, is a growing public health challenge amid the rapidly ageing population. As there are no approved drugs that target sarcopenia, it has become increasingly urgent to identify promising pharmaco...

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Autores principales: Liang, Shuang, Liu, Danyang, Xiao, Zhengwu, Greenbaum, Jonathan, Shen, Hui, Xiao, Hongmei, Deng, Hongwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145476/
https://www.ncbi.nlm.nih.gov/pubmed/37111364
http://dx.doi.org/10.3390/ph16040607
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author Liang, Shuang
Liu, Danyang
Xiao, Zhengwu
Greenbaum, Jonathan
Shen, Hui
Xiao, Hongmei
Deng, Hongwen
author_facet Liang, Shuang
Liu, Danyang
Xiao, Zhengwu
Greenbaum, Jonathan
Shen, Hui
Xiao, Hongmei
Deng, Hongwen
author_sort Liang, Shuang
collection PubMed
description Sarcopenia, characterized by age-related loss of muscle mass, strength, and decreased physical performance, is a growing public health challenge amid the rapidly ageing population. As there are no approved drugs that target sarcopenia, it has become increasingly urgent to identify promising pharmacological interventions. In this study, we conducted an integrative drug repurposing analysis utilizing three distinct approaches. Firstly, we analyzed skeletal muscle transcriptomic sequencing data in humans and mice using gene differential expression analysis, weighted gene co-expression analysis, and gene set enrichment analysis. Subsequently, we employed gene expression profile similarity assessment, hub gene expression reversal, and disease-related pathway enrichment to identify and repurpose candidate drugs, followed by the integration of findings with rank aggregation algorithms. Vorinostat, the top-ranking drug, was also validated in an in vitro study, which demonstrated its efficacy in promoting muscle fiber formation. Although still requiring further validation in animal models and human clinical trials, these results suggest a promising drug repurposing prospect in the treatment and prevention of sarcopenia.
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spelling pubmed-101454762023-04-29 Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans Liang, Shuang Liu, Danyang Xiao, Zhengwu Greenbaum, Jonathan Shen, Hui Xiao, Hongmei Deng, Hongwen Pharmaceuticals (Basel) Article Sarcopenia, characterized by age-related loss of muscle mass, strength, and decreased physical performance, is a growing public health challenge amid the rapidly ageing population. As there are no approved drugs that target sarcopenia, it has become increasingly urgent to identify promising pharmacological interventions. In this study, we conducted an integrative drug repurposing analysis utilizing three distinct approaches. Firstly, we analyzed skeletal muscle transcriptomic sequencing data in humans and mice using gene differential expression analysis, weighted gene co-expression analysis, and gene set enrichment analysis. Subsequently, we employed gene expression profile similarity assessment, hub gene expression reversal, and disease-related pathway enrichment to identify and repurpose candidate drugs, followed by the integration of findings with rank aggregation algorithms. Vorinostat, the top-ranking drug, was also validated in an in vitro study, which demonstrated its efficacy in promoting muscle fiber formation. Although still requiring further validation in animal models and human clinical trials, these results suggest a promising drug repurposing prospect in the treatment and prevention of sarcopenia. MDPI 2023-04-18 /pmc/articles/PMC10145476/ /pubmed/37111364 http://dx.doi.org/10.3390/ph16040607 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liang, Shuang
Liu, Danyang
Xiao, Zhengwu
Greenbaum, Jonathan
Shen, Hui
Xiao, Hongmei
Deng, Hongwen
Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans
title Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans
title_full Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans
title_fullStr Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans
title_full_unstemmed Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans
title_short Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans
title_sort repurposing approved drugs for sarcopenia based on transcriptomics data in humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145476/
https://www.ncbi.nlm.nih.gov/pubmed/37111364
http://dx.doi.org/10.3390/ph16040607
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