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- Upstream of precise disease models for better downstream decision makingPublication . Duarte, Ana; Moreira, Luciana; Ribeiro, Diogo; Bragança, José; Amaral, OlgaInborn errors of metabolism are a common cause of inherited diseases. Diseases of carbohydrate metabolism pathway include lysosomal storage diseases (LSDs), which are a significant subgroup with approximately 70 LSDs. Grouped according to their defective lysosomal proteins and pathways they are usually characterized by intralysosomal accumulation of substrate. Accumulation may occur at different levels in diverse types of cells, some of which are of difficult access. Patient, molecular, cell and tissue heterogeneity hinders the development of further therapeutic approaches. We are currently establishing human Induced Pluripotent Stem Cells (iPSCs) from fibroblasts of LSDs patients and controls. The use of disease-specific cell models, mimicking the cell-target of the specific disease, may help to appropriately study the pathogenesis as well as the therapeutics. Integrating new techniques in the work pipeline for the establishment of models may lead to more accurate models while ensuring the safeguard of the patient’s background. Advanced technologies like microarray and NGS profiling add to the traditional techniques such as Immunofluorescence, directed sequencing and conventional cytogenetics. As in the diagnosis process, we may better understand the prognosis, and contribute to cost avoidance, by combining genomic and protein profiling checkpoints in the cell-model establishment pipeline. The investment in the upstream checkpoints might prove to be helpful in ensuring the integrity of the cell models.
- Induced pluripotent stem cell line (INSAi002-A) from a Fabry Disease patient hemizygote for the rare p.W287X mutationPublication . Duarte, Ana; Ribeiro, Diogo; Santos, Renato; Moreira, Luciana; Bragança, José; Amaral, OlgaFabry Disease (FD) is a multisystemic X-linked disorder that belongs to the group of lysosomal storage disorders (LSDs). Causal mutations on alpha-galactosidase A (α-Gal A) commonly lead to abnormal protein and consequently to FD. Since it is an X-linked disease, males are primarily affected. This work describes the generation of induced Pluripotent Stem Cells (iPSCs) from skin fibroblasts from a FD patient, using non-integrative episomal vectors. Differentiation of iPSCs can be applied to generate a variety of cell types with high degree of genetic complexity that would otherwise be difficult to obtain.
- Induced pluripotent stem cell line (INSAi001-A) from a Gaucher disease type 3 patient compound heterozygote for mutations in the GBA1 genePublication . Duarte, Ana Joana; Ribeiro, Diogo; Santos, Renato; Moreira, Luciana; Bragança, José; Amaral, OlgaGaucher Disease (GD) type 3 is a neurological form of a multisystemic autosomal recessive disorder belonging to the group of lysosomal storage diseases. Causal mutations in the glucocerebrosidase 1 (GBA1) commonly lead to abnormal protein and GD, heterozygosity is a genetic risk factor for Parkinson's disease. This work describes the use of a non-integrative approach using Sendai Virus delivery to establish induced Pluripotent Stem Cells (iPSCs) from fibroblasts from a GD type 3 patient. Differentiation of iPSCs can be employed to generate a variety of complex cell types with a high degree of genetic complexity that would otherwise be unattainable.