Characterization of the electrophysiological properties of human pluripotent stem cell derived neurons (HPSC) from fragile x syndrome patients

Abstract

Fragile X Syndrome (FXS) is an X-linked disorder and the most common form of inherited intellectual disability and autism. It is caused by an increased CGG triplet repeat mutation in the 5’ UTR of the Fragile X mental retardation 1 (FMR1) gene, thereby silencing the gene and subsequent loss of its product. Data from animal models suggest that FMRP expression is necessary for proper neuronal development and normal synaptic physiology. Clinical investigations to develop FXS specific treatments based on the above preclinical findings have limited success. Thus, it is imperative to look into more human-based FXS in vitro models using neural progenitor cells and compare them with the existing animal models of FXS. The neurons derived from human stem cells of patients with FXS can therefore serve as an invaluable model to study the progression of the symptoms of FXS in vitro and subsequently help in developing new therapies. In my PhD, I focused on studying the functional properties of human stem cell derived FXS neurons and rescuing the potential defects.