Drug Repositioning Applied to Cardiovascular Disease in Mucopolysaccharidosis

Gerda Cristal Villalba Silva; Thiago Steindorff; Roselena Silvestri Schuh; Natalia Cardoso Flores; Ursula Matte

doi:10.3390/life12122085

Drug Repositioning Applied to Cardiovascular Disease in Mucopolysaccharidosis

Life (Basel). 2022 Dec 12;12(12):2085. doi: 10.3390/life12122085.

Authors

Gerda Cristal Villalba Silva¹, Thiago Steindorff^{1

2

3}, Roselena Silvestri Schuh^{2

4}, Natalia Cardoso Flores^{1

2

3}, Ursula Matte^{1

2

5}

Affiliations

¹ Bioinformatics Core, Hospital de Clinicas de Porto Alegre, Ramiro Barcelos, Porto Alegre 2350, RS, Brazil.
² Gene Therapy Center, Hospital de Clinicas de Porto Alegre, Ramiro Barcelos, Porto Alegre 2350, RS, Brazil.
³ Biomedical Sciences School, Institute of Health Sciences, UFRGS, Ramiro Barcelos, Porto Alegre 2600, RS, Brazil.
⁴ Pharmaceutical Sciences Graduate Program, UFRGS, Avenida Ipiranga, Porto Alegre 2752, RS, Brazil.
⁵ Genetics and Molecular Biology Graduate Program, UFRGS, Av. Bento Gonçalves, Porto Alegre 9500, RS, Brazil.

Abstract

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.

Keywords: bioinformatics; cardiovascular diseases; drug repositioning; gene expression analysis; lysosomal storage diseases; systems pharmacology.

Grants and funding

This research was funded by Hospital de Clínicas de Porto Alegre (GCVS post-doctoral scholarship) and FIPE (2022-0216). We also thank Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq for the grants provided for RS (grant number 403587/2021-2) and UM (grant number 312714/2018-1).