Laboratory of Stem Cell and Developmental Neurobiology, VIB-KU Leuven Center for Brain & Disease Research, 3000 Leuven, Belgium.
Center for Human Genetics, University Hospitals Leuven, 3000 Leuven, Belgium.
Int J Mol Sci. 2022 Jun 9;23(12):6476. doi: 10.3390/ijms23126476.
Intellectual disability (ID) is characterized by deficits in conceptual, social and practical domains. ID can be caused by both genetic defects and environmental factors and is extremely heterogeneous, which complicates the diagnosis as well as the deciphering of the underlying pathways. Multiple scientific breakthroughs during the past decades have enabled the development of novel ID models. The advent of induced pluripotent stem cells (iPSCs) enables the study of patient-derived human neurons in 2D or in 3D organoids during development. Gene-editing tools, such as CRISPR/Cas9, provide isogenic controls and opportunities to design personalized gene therapies. In practice this has contributed significantly to the understanding of ID and opened doors to identify novel therapeutic targets. Despite these advances, a number of areas of improvement remain for which novel technologies might entail a solution in the near future. The purpose of this review is to provide an overview of the existing literature on scientific breakthroughs that have been advancing the way ID can be studied in the human brain. The here described human brain models for ID have the potential to accelerate the identification of underlying pathophysiological mechanisms and the development of therapies.
智力障碍（ID）的特征是在概念、社会和实践领域存在缺陷。ID 既可以由遗传缺陷引起，也可以由环境因素引起，而且极其异质，这使得诊断以及潜在途径的破译变得复杂。过去几十年的多项科学突破使新型 ID 模型的开发成为可能。诱导多能干细胞（iPSC）的出现使得在发育过程中能够在 2D 或 3D 类器官中研究患者来源的人类神经元。基因编辑工具，如 CRISPR/Cas9，提供同基因对照并为设计个性化基因治疗提供了机会。实际上，这对 ID 的理解做出了重大贡献，并为确定新的治疗靶点打开了大门。尽管取得了这些进展，但仍有一些需要改进的领域，新的技术可能在不久的将来提供解决方案。本综述的目的是提供对推进 ID 在人类大脑中研究的科学突破的现有文献的概述。这里描述的 ID 人类大脑模型有可能加速确定潜在的病理生理机制和开发治疗方法。
