Drug Repositioning Applied to Cardiovascular Disease in Mucopolysaccharidosis.
Gerda Cristal Villalba SilvaThiago SteindorffRoselena Silvestri SchuhNatalia Cardoso FloresUrsula da Silveira MattePublished in: Life (Basel, Switzerland) (2022)
Mucopolysaccharidoses (MPS) are genetic metabolic diseases characterized by defects in the activity of lysosomal hydrolases. In MPS, secondary cell disturbance affects pathways related to cardiovascular disorders. Hence, the study aimed to identify MPS-related drugs targeting cardiovascular disease and select a list of drugs for repositioning. We obtained a list of differentially expressed genes and pathways. To identify drug perturbation-driven gene expression and drug pathways interactions, we used the CMAP and LINCS databases. For molecular docking, we used the DockThor web server. Our results suggest that pirfenidone and colchicine are promising drugs to treat cardiovascular disease in MPS patients. We also provide a brief description of good practices for the repositioning analysis. Furthermore, the list of drugs and related MPS-enriched genes could be helpful to new treatments and considered for pathophysiological studies.
Keyphrases
- cardiovascular disease
- molecular docking
- gene expression
- drug induced
- genome wide
- end stage renal disease
- type diabetes
- dna methylation
- ejection fraction
- primary care
- healthcare
- newly diagnosed
- chronic kidney disease
- molecular dynamics simulations
- single cell
- idiopathic pulmonary fibrosis
- machine learning
- adverse drug
- mesenchymal stem cells
- bioinformatics analysis
- coronary artery disease
- cell therapy
- replacement therapy
- electronic health record