Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, SMS, FMHS, University of Auckland, Auckland, New Zealand.
Adv Exp Med Biol. 2020;1266:57-69. doi: 10.1007/978-981-15-4370-8_5.
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.
亨廷顿病（HD）是一种遗传性神经退行性疾病，其特征是严重致残的运动、认知和精神症状三联征。虽然细胞死亡发生在许多脑区，但纹状体中的 GABA 能中间神经元（MSNs）经历优先和广泛的退化。与大多数神经退行性疾病不同，HD 是由单个基因突变引起的，导致 CAG 重复扩展和产生突变亨廷顿蛋白（mHTT）。尽管 1993 年已经确定了导致 HD 的突变，但目前尚无针对 HD 的疾病修饰治疗方法。HD 治疗的一种潜在策略是开发基于细胞的疗法。基于细胞的疗法旨在通过替换丢失的神经元以及提供神经营养支持来防止进一步退化，从而恢复神经元回路和功能。为了成功恢复 HD 中的基底神经节功能，基于细胞的疗法需要重建由 MSN 广泛退化破坏的复杂信号网络。本章将讨论使用胎儿组织移植物、多能干细胞、神经干细胞和体细胞重编程来开发治疗 HD 的基于细胞的疗法的潜力。
