Repurposing Approved Drugs for Sarcopenia Based on Transcriptomics Data in Humans.
Shuang LiangDanyang LiuZhengwu XiaoJonathan GreenbaumHui ShenHongmei XiaoHong-Wen DengPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
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.
Keyphrases
- skeletal muscle
- genome wide identification
- public health
- gene expression
- copy number
- genome wide
- clinical trial
- single cell
- dna methylation
- insulin resistance
- physical activity
- endothelial cells
- electronic health record
- drug induced
- magnetic resonance
- randomized controlled trial
- type diabetes
- big data
- machine learning
- magnetic resonance imaging
- rna seq
- deep learning
- current status
- global health
- combination therapy