Induced pluripotent stem cells as tools for disease modelling and drug discovery in Alzheimer's disease
The use of induced pluripotent stem cells (iPSCs), whereby a patient's somatic cells can be reprogrammed to a pluripotent state by the forced expression of a defined set of transcription factors, has the potential to enable in vitro disease modelling and be used for drug discovery programs. Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that leads to a decline in memory and cognition. Fibroblasts were taken from AD patients (or non-AD controls) and cultured under specific conditions to generate iPSCs which were then provided with growth factors to allow differentiation into neurons. While AD-iPSCs were morphologically indistinguishable from control-iPSCs, differentiated cells showed differing responses to cellular stresses. Since these cells are derived from individual patients, the use of iPSCs have provided novel insights into disease pathogenesis, providing information on an individual's variations in the disease process and their cellular response to drugs. Using this system we have identified a number of drugs that protect AD neurons against the damaging effects of oxidative stress.