Animal and cellular models have been developed to study neurodegenerative diseases, but do not always epitomize the pathology of human diseases. While some insight into neurodegenerative disorders and their cellular mechanisms has been gained from the study of post-mortem human brain tissue, this source does not dynamically represent disease pathogenesis.Patient-specific induced pluripotent stem cells (iPSC) recapitulate the genotype and phenotype of their parental somatic cells and can be used to model disease in vitro. Patient-specific neuronal derivatives are easily accessible sources of human neurons for studying the mechanisms of neurodegenerative diseases.

The objectve of this study is to create an in vitro human neural cell model using induced pluripotent stem cells (iPSC). derived from fragile-X associated tremor/ataxia syndrome (FXTAS) patient’s fibroblasts. In FXTAS the affected gene, FMR1, is located on the X-chromosome. Because FXTAS patient-derived iPSC undergo X-inactivation upon differentiation into neurons, both diseased and normal iPSC lines can be derived from a female patient’s fibroblasts and compared. We aim to define the FXTAS phenoytype in human neurons derived from these
iPSC lines as a basis for the further understanding of the cellular mechanisms of FXTAS-mediated neurodegeneration as well as the future development of targeted therapeutic agents for the treatment of the disorder.