Patient-specific molecular mechanisms of Fragile X Syndrome pathogenesis and Fragile-X associated phenotypes

Fragile X Syndrome (FXS) is the leading cause of inherited mental retardation, intellectual disability, and is the single most common cause of autism spectrum disorders.
The general objective of the project is the investigation of the genetic and epigenetic modifications of FMR1 locus during the ealy embrionic stage of neural development by means of an in vitro patient-specific human model formed neural forebrain organoids. Human model based on patient-specific stem cell has the potential to reproduce the neural development from a pre-implantation embryonic stage to a late neural differentiation in brain organoids, which recapitulate the linage-specific epigenetic regulation and pathogenetic modifications of FMR1 locus.
We hypothesize that the investigation of the early phase of human neural development in human model of Fragile X Syndrome (FXS) and Fragile X-associated tremor Ataxia Syndrome (FXTAS) are fundamental for the establishment of a therapeutic strategy.