Abstract:
Huntington\'s disease (HD) is a hereditary, neurodegenerative disorder characterized by a triad of symptoms: motor, cognitive and psychiatric. HD is caused by a genetic mutation, expansion of the CAG repeat in the huntingtin gene, which results in loss of medium spiny neurons (MSNs) of the striatum. Cell replacement therapy (CRT) has emerged as a possible therapy for HD, aiming to replace those cells lost to the disease process and alleviate its symptoms. Initial pre-clinical studies used primary fetal striatal cells to provide proof-of-principal that CRT can bring about functional recovery on some behavioral tasks following transplantation into HD models. Alternative donor cell sources are required if CRT is to become a viable therapeutic option and human pluripotent stem cell (hPSC) sources, which have undergone differentiation toward the MSNs lost to the disease process, have proved to be strong candidates. The focus of this chapter is to review work conducted on the functional assessment of animals following transplantation of hPSC-derived MSNs. We discuss different ways that graft function has been assessed, and the results that have been achieved to date. In addition, this chapter presents and discusses challenges that remain in this field.
摘要:
亨廷顿病(HD)是一种遗传性疾病,神经退行性疾病的特点是三位一体的症状:运动,认知和精神病学。HD是由基因突变引起的,亨廷顿基因中CAG重复序列的扩增,这导致纹状体的中等多刺神经元(MSN)的损失。细胞替代疗法(CRT)已成为HD的一种可能疗法,旨在替换那些在疾病过程中丢失的细胞并减轻其症状。最初的临床前研究使用原代胎儿纹状体细胞来提供主要证据,证明CRT可以在移植到HD模型中后在某些行为任务上带来功能恢复。如果CRT要成为可行的治疗选择和人类多能干细胞(hPSC)来源,则需要替代的供体细胞来源。它们已经经历了向疾病过程中丢失的MSN的分化,被证明是强有力的候选人。本章的重点是回顾在hPSC衍生的MSN移植后对动物进行功能评估的工作。我们讨论了评估移植物功能的不同方法,以及迄今取得的成果。此外,本章介绍并讨论了该领域仍然存在的挑战。