Induced pluripotent stem cells-derived neurons from patients with Friedreich ataxia exhibit differential sensitivity to resveratrol and nicotinamide

Autor:	Aurélien Bayot, Pauline Georges, Pierre Rustin, Maria-Gabriela Boza-Moran, Laetitia Aubry, Marc Peschanski, Cécile Martinat, Jacqueline Gide, Georges Arielle Pêche, Benjamin Forêt
Přispěvatelé:	Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	Niacinamide 0301 basic medicine Cell type Ataxia Cell Survival [SDV]Life Sciences [q-bio] Science Induced Pluripotent Stem Cells Cell Apoptosis Biology Resveratrol Article Translational Research Biomedical 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pluripotent stem cells Iron-Binding Proteins medicine Humans Induced pluripotent stem cell Cells Cultured Neurons Multidisciplinary Drug discovery Gene Expression Profiling Lymphoblast Neurodegenerative diseases Fibroblasts 3. Good health Phenotype 030104 developmental biology medicine.anatomical_structure chemistry Friedreich Ataxia Drug Design Karyotyping Frataxin biology.protein Cancer research Medicine medicine.symptom 030217 neurology & neurosurgery
Zdroj:	Scientific Reports, Vol 9, Iss 1, Pp 1-7 (2019) Scientific Reports Scientific Reports, 2019, 9 (1), pp.14568. ⟨10.1038/s41598-019-49870-y⟩
ISSN:	2045-2322
Popis:	Translation of pharmacological results from in vitro cell testing to clinical trials is challenging. One of the causes that may underlie these discrepant results is the lack of the phenotypic or species-specific relevance of the tested cells; today, this lack of relevance may be reduced by relying on cells differentiated from human pluripotent stem cells. To analyse the benefits provided by this approach, we chose to focus on Friedreich ataxia, a neurodegenerative condition for which the recent clinical testing of two compounds was not successful. These compounds, namely, resveratrol and nicotinamide, were selected because they had been shown to stimulate the expression of frataxin in fibroblasts and lymphoblastoid cells. Our results indicated that these compounds failed to do so in iPSC-derived neurons generated from two patients with Friedreich ataxia. By comparing the effects of both molecules on different cell types that may be considered to be non-relevant for the disease, such as fibroblasts, or more relevant to the disease, such as neurons differentiated from iPSCs, a differential response was observed; this response suggests the importance of developing more predictive in vitro systems for drug discovery. Our results demonstrate the value of utilizing human iPSCs early in drug discovery to improve translational predictability.
Databáze:	OpenAIRE
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