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
- type diabetes
- dna methylation
- healthcare
- primary care
- end stage renal disease
- ejection fraction
- single cell
- cardiovascular risk factors
- molecular dynamics simulations
- prognostic factors
- idiopathic pulmonary fibrosis
- metabolic syndrome
- cardiovascular events
- copy number
- replacement therapy
- mesenchymal stem cells
- big data
- small molecule
- bone marrow
- transcription factor
- artificial intelligence
- case control