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cc-by (c) Benetó, Noelia et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/174369

Neuronal and astrocytic differentiation from Sanfilippo C syndrome iPSCs for disease modeling and drug development

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Sanfilippo syndrome type C (mucopolysaccharidosis IIIC) is an early-onset neurodegenerative lysosomal storage disorder, which is currently untreatable. The vast majority of studies focusing on disease mechanisms of Sanfilippo syndrome were performed on non-neural cells or mouse models, which present obvious limitations. Induced pluripotent stem cells (iPSCs) are an efficient way to model human diseases in vitro. Recently developed transcription factor-based differentiation protocols allow fast and efficient conversion of iPSCs into the cell type of interest. By applying these protocols, we have generated newneuronal and astrocyticmodels of Sanfilippo syndrome using our previously established disease iPSC lines. Moreover, our neuronal model exhibits disease-specific molecular phenotypes, such as increase in lysosomes and heparan sulfate. Lastly, we tested an experimental, siRNA-based treatment previously shown to be successful in patients' fibroblasts and demonstrated its lack of efficacy in neurons. Our findings highlight the need to use relevant human cellular models to test therapeutic interventions and shows the applicability of our neuronal and astrocyticmodels of Sanfilippo syndrome for future studies on disease mechanisms and drug development.

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BENETÓ, Noelia, COZAR, Mónica, CASTILLA-VALLMANYA, Laura, ZETTERDAHL, Oskar g., SACULTANU, Madalina, SEGUR-BAILACH, Eulalia, GARCÍA-MORANT, María, RIBES RUBIÓ, Maria antònia, AHLENIUS, Henrik, GRINBERG VAISMAN, Daniel raúl, VILAGELIU I ARQUÉS, Lluïsa, CANALS MONTFERRER, Isaac. Neuronal and astrocytic differentiation from Sanfilippo C syndrome iPSCs for disease modeling and drug development. _Journal of Clinical Medicine_. 2020. Vol. 9, núm. 644. [consulta: 20 de gener de 2026]. ISSN: 2077-0383. [Disponible a: https://hdl.handle.net/2445/174369]

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