Current opinion on pluripotent stem cell technology in Gaucher's disease: challenges and future prospects

Abstract

Gaucher's disease (GD) is a rare autosomal recessive genetic disorder caused by mutations in the GBA1 gene. Mutations in the gene lead to the deficiency of glucocerebrosidase, an enzyme that helps in the breakdown of glucosylceramide (GlcCer) into ceramide and glucose. The lack of the enzyme causes GlcCer accumulation in macrophages, resulting in various phenotypic characteristics of GD. The currently available therapies, including enzyme replacement therapy and substrate reduction therapy, only provide symptomatic relief. However, they grapple with limitations in efficacy, accessibility, and potential side effects. These observations laid the foundation to search for new approaches in the management of GD. Induced pluripotent stem cells (iPSCs) technology emerges as a beacon of hope, offering novel avenues for future GD therapies. The true magic of iPSCs lies in their ability to differentiate into various cell types. By reprogramming patient-derived cells into iPSCs, researchers can generate personalized models that recapitulate the genetic and phenotypic characteristics of the GD. These models are valuable tools for dissecting intricate disease pathways, developing novel therapeutic targets, and enhancing the drug development process for GD. This review emphasizes the significance of iPSCs technology in GD management. Further, it addresses several challenges that are being encountered in the application of iPSC technology in the management of GD. In addition, it provides several insights into the future aspects of iPSC technology in the management of GD.

Keywords: Gaucher’s disease; Gaucher’s disease model; Glucocerebrosidase; Glucosylceramide; Human induced pluripotent stem cell; Wnt; mTOR.