Cell Replacement Therapy for Huntington's Disease.

Abstract

Huntington's disease (HD) is an inherited neurodegenerative disorder which is characterised by a triad of highly debilitating motor, cognitive, and psychiatric symptoms. While cell death occurs in many brain regions, GABAergic medium spiny neurons (MSNs) in the striatum experience preferential and extensive degeneration. Unlike most neurodegenerative disorders, HD is caused by a single genetic mutation resulting in a CAG repeat expansion and the production of a mutant Huntingtin protein (mHTT). Despite identifying the mutation causative of HD in 1993, there are currently no disease-modifying treatments for HD. One potential strategy for the treatment of HD is the development of cell-based therapies. Cell-based therapies aim to restore neuronal circuitry and function by replacing lost neurons, as well as providing neurotropic support to prevent further degeneration. In order to successfully restore basal ganglia functioning in HD, cell-based therapies would need to reconstitute the complex signalling network disrupted by extensive MSN degeneration. This chapter will discuss the potential use of foetal tissue grafts, pluripotent stem cells, neural stem cells, and somatic cell reprogramming to develop cell-based therapies for treating HD.