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Title: Neuronal and astrocytic differentiation from Sanfilippo C syndrome iPSCs for disease modeling and drug development
Author: Benetó, Noelia
Cozar, Mónica
Castilla-Vallmanya, Laura
Zetterdahl, Oskar G.
Sacultanu, Madalina
Segur-Bailach, Eulalia
García-Morant, María
Ribes, Antonia
Ahlenius, Henrik
Grinberg Vaisman, Daniel Raúl
Vilageliu i Arqués, Lluïsa
Canals Montferrer, Isaac
Keywords: Malalties del sistema nerviós
Malalties hereditàries
Nervous system Diseases
Genetic diseases
Issue Date: 28-Feb-2020
Publisher: MDPI
Abstract: 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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It is part of: Journal of Clinical Medicine, 2020, vol. 9, num. 644
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ISSN: 2077-0383
Appears in Collections:Articles publicats en revistes (Genètica, Microbiologia i Estadística)
Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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