IPSC models of neurodegenerative disease

Abstract: In the period since the publication Yamanaka’s seminal papers in 2006/2007 induced pluripotent stem cell technology has transformed our approaches to disease modelling. iPSC technology places patients and human genetics at the centre of the disease modelling process. This has been especially true for the large expansion in IPSC models for neurodegenerative diseases that we will discuss in relation to Huntington’s disease (HD). HD is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG repeat in the huntingtin gene, HTT. The length of the CAG repeat is inversely correlated with age at motor onset but other factors influence onset including genetic variation elsewhere in the genome. When differentiated into neurons and glia HD IPSC-derived models recapitulate many of the cell and molecular pathologies associated with the disease and studies are now revealing new disease phenotypes and mechanisms, with new prospects for drug development. In this paper we will give an overview of progress made, of the IPSC resources available, and how new technologies and extended knowledge of HD genetics are impacting on the next generation of IPSC models.

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