OBJECTIVES : Gaucher Disease (GD,OMIM #230800, ORPHA355) is a rare, autosomal, recessive genetic disease caused by mutations in the GBA1 gene, located on chromosome 1 (1q21). This leads to a markedly decreased activity of the lysosomal enzyme, glucocerebrosidase (GCase, also called glucosylceramidase or acid β-glucosidase, EC: 4.2.1.25), which hydrolyzes glucosylceramide (GlcCer) into ceramide and glucose. Three clinical forms have been identified: type 1, the most common and typically causes no neurological damage, whereas types 2 and 3 are characterized by neurological impairment. This study aimed to screen bio-targets of Type-1 Gaucher Disease (GD1, ORPHA77259) and to identify related drug molecules.

METHODS : The dataset GSE15568 included the gene expression profiles of 5 GD1 and 4 controls, was downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened out using GEO2R. Hierarchical clustering and differences between the groups analysis were conducted for confirming these DEGs. Protein-Protein Interactions (PPI) was constructed using STRING. The DEGs were then entered into the Drug Repurposing Hub and DrugBank and related drug molecules were retrieved.

RESULTS : The genes linked with GD1 were found to be GBA, JAK2, MAPK14, DHX9, STAT1, IL1R1, CD44, EML4, IL6ST, FN1, EEA1, HBP1 and MCL1. The drugs with possibility of therapeutic repurposing, targeting these genes were found to be Anakinra, Hyaluronic acid, Bivatuzumab, Lanoteplase, Ocriplasmin and CKD-712.

CONCLUSIONS : Drug repurposing is an unconventional drug discovery approach to explore new therapeutic benefits of existing, shelved and the drugs. Computational techniques circumvent expensive initial drug discovery phases and contemporary repurposing tools offer new molecular mechanisms of existing drugs. GD1 can often limit quality of life and is often associated with considerable morbidity. Therapeutic options for the same are limited which poses a threat to the lives of these patients. Drug repurposing proposes a new window of hope which could help make their lives better.