The prevalence of late-onset neurodegenerative disorders such as Alzheimer’s and
Parkinson’s disease is increasing alarmingly worldwide but their causes remain largely unknown. In
order to study the pathogenesis of these diseases researchers use a variety of models from cell culture
through to full organisms. As the complexity of the model system increases so does the potential
variables that can confound experimental results and interpretation. Transgenic animal models are the
workhorses of disease research but they have been purposefully intra-bred to remove their genetic
variability, a major factor in human neurodegenerative disease. Prior to stem cell advances, researchers
could obtain differentiated cell types such as fibroblasts from patients and these had reasonable
longevity in the laboratory. However it was questionable how much fibroblasts could tell us about the
relative susceptibilities of cells in the human brain. Embryonic stem cell lines provided the flexibility to
produce all the different cell types of the body including neurons but they were derived from a limited
number of individuals. It was the discovery of induced pluripotency by Yamanaka and colleagues that
allowed neurons to be produced from a number of patients and unaffected controls. Now individual
genetic variability could be incorporated into our experimental paradigms. Looking forward, induced
pluripotent stem cells (iPSC) can be perturbed with putative toxins to re-create the natural history of a
disease. This in vitro phenotype can then be used for the high throughput screening of therapeutic
agents. The latter is akin to a “cure in a dish”.
Keywords: Embryonic stem cells, induced pluripotent stem cells, neurodegenerative diseases, disease
modelling, differentiation, drug secreening.
