Human induced pluripotent stem cells (hiPSCs) derived from patients with neurological disease are an invaluable source to study the development of central nervous system disorders such as epilepsy. In a novel approach, we will investigate if hiPSCs from epilepsy patients carrying genetic variants of uncertain significance may help elucidate pathogenicity and response to antiseizure medication, paving a way for a rapid, simple but revolutionary tool to deliver precision medicine diagnosis and treatment.
– To develop an hiPSC bank from patients with known pathogenic germline mutations causing epilepsy and characterise their histology, neurophysiology and response to antiseizure drugs. Subsequently, to compare skin fibroblast-derived hiPSCs with hiPSC derived from nasal mucosal swabs.
– To establish if hiPSCs grown on multielectrode arrays could become a first stage screening tool for novel mutations of uncertain significance.
– To engineer hiPSC with mammalian Target of Rapamycin (mTOR) mutations from patients with focal cortical dysplasia (FCD) as novel platform to test mTOR inhibitor treatment and predict surgical outcome.
HiPSC derivation, histological and neurophysiological in vitro techniques, deep phenotyping and epidemiology of genetic epilepsy patients, database and Biobank development.
Year 1: Acquisition of Technical (hiPSC culture, histology and in vitro neurophysiology) and Clinical Skills (Deep phenotyping of Epilepsy patients, Genetic epilepsy clinics)
Year 2: HiPSC Bank Development (; detailed histological, neurophysiological and pharmacological characterisation)
Year 3: Translating Results from Bench to Bedside (Comparing experimental and clinical outcomes, development of diagnostic tool for predicting network effect of genetic mutations and treatment efficacy).