iPSC-based drug screening for Huntington's disease

Brain Res. 2016 May 1;1638(Pt A):42-56. doi: 10.1016/j.brainres.2015.09.020. Epub 2015 Sep 30.

Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. The disease generally manifests in middle age with both physical and mental symptoms. There are no effective treatments or cures and death usually occurs 10-20 years after initial symptoms. Since the original identification of the Huntington disease associated gene, in 1993, a variety of models have been created and used to advance our understanding of HD. The most recent advances have utilized stem cell models derived from HD-patient induced pluripotent stem cells (iPSCs) offering a variety of screening and model options that were not previously available. The discovery and advancement of technology to make human iPSCs has allowed for a more thorough characterization of human HD on a cellular and developmental level. The interaction between the genome editing and the stem cell fields promises to further expand the variety of HD cellular models available for researchers. In this review, we will discuss the history of Huntington's disease models, common screening assays, currently available models and future directions for modeling HD using iPSCs-derived from HD patients. This article is part of a Special Issue entitled SI: PSC and the brain.

Keywords: Drug screening; Huntington׳s disease; Induced pluripotent stem cells; Phenotypes; Stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Line
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Humans
  • Huntington Disease / drug therapy*
  • Huntington Disease / genetics
  • Huntington Disease / metabolism
  • Induced Pluripotent Stem Cells / drug effects*
  • Induced Pluripotent Stem Cells / transplantation