The identification of various genetic susceptibility loci associated with neurodegenerative diseases, such as Frontotemporal Dementia, opens up new possibilities for understanding the pathogenic mechanisms associated with the disease. In this project, we develop induced pluripotent stem cell lines (CMPi) from blood cells of patients that carry allelic variants in genes of interest. We used the CRISPR-Cas9 gene editing system to generate cells identical to the original ones with the corrected mutation. Through the directed differentiation of these cells to neural lineages in 2D culture systems, together with the technology to generate three-dimensional structures called “brain organoids”, we seek to identify in human models how pathogenic variants contribute to the initiation and progression of Frontotemporal Dementia. Since age is a main risk factor in the development of dementias, we are interested in elucidating the role of molecular pathways associated with aging in disease development. This knowledge will contribute to the identification of potential therapeutic targets to prevent or treat the disease.
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