Tool for Researchers
Over the last decade it has become possible to create patient-specific disease models for the purposes of studying biology and testing potential treatments. Patient-derived models include: fibroblast cells derived from skin samples (patient-derived fibroblasts [PDFs]), induced pluripotent stem cells (iPSCs) created by reprogramming fibroblasts, and specialized cells, such as neurons, created from iPSCs through a process called differentiation. The key advantage of such patient-derived models is that they contain the same genome as the patient, and as such, in optimized experimental assays, glycosylation defects characteristic of CDG can be studied. Non-patient derived cells can be engineered to express mutated versions of CDG genes to study their function.
(PDFs) have previously been used to study CDGs. Laboratory studies are planned to improve patient-derived models for SRD5A3-CDG, including PDFs and iPSC based models. For SRD5A3-CDG, patient-derived models will help researchers understand the impact of polyprenol reductase enzyme deficiency and also serve as an early proving ground for the use of supplements, drugs, and gene therapies as potential therapeutic treatments.
Current research into SRD5A3-CDG includes the development of worms and zebrafish with mutations in the SRD5A3 gene. SRD5A3-deficient worms exhibit a slow motility phenotype (unpublished data). Researchers previously generated knockout mice with whole-gene mutations in SRD5A3, but these mice died in utero as the mutation was too severe for the mouse embryo to survive. More recently, researchers in the United States and France have been working on genetically modified mice that have SRD5A3 mutations limited to the cerebellum region of their brain. These mice are viable, show CDG symptoms in the brain, and are part of planned studies for new experimental treatments.