Modeling neurodegenerative diseases with human pluripotent stem cells

Abstract

The discovery of human pluripotent stem cells has enabled the development of assays to model human disease in vitro. The research described in this thesis has focused on modeling Amyotrophic Lateral Sclerosis and Lesch Nyhan Syndrome using pluripotent stem cells. Chapter 1 contains the aim and outline of this thesis, Chapter 2 is introduction to the field and provides an overview of recent advances in stem cell modeling of Amyotrophic Lateral Sclerosis (ALS). Chapter 3 contains an introduction to the field of X-chromosome inactivation. In Chapter 4 we identify the Prostaglandin D2 DP1 receptor (DP1) as a therapeutic target for ALS and more generally validate that insights found in stem cell models of disease can be validated in vivo. In Chapter 5, we address whether non-steroidal anti-inflammatory drugs (NSAIDs) affect survival of motor neurons in ALS. In Chapter 6, we develop a stem cell assay to model Lesch Nyhan Syndrome (LNS). Finally, Chapter 7 is the general discussion of the work and contains a short perspective of the future.