3Dnamics, Inc., Baltimore, MD, USA.
Methods Mol Biol. 2022;2474:93-105. doi: 10.1007/978-1-0716-2213-1_10.
The road to discover novel therapeutics for mental and neurological disorders has been severely hampered by the lack of access to relevant testing platforms. Currently, roughly 0.1% of drugs that show promise in preclinical testing make it to Phase I clinical trials, and 90% of those drugs go on to fail FDA approval. One of the reasons responsible for this low success rate is that conventional two-dimensional (2D) cell culture models are not accurate enough predictors of how drugs will work in humans. Three-dimensional (3D) brain organoids differentiated from induced pluripotent stem cells (iPSCs) to resemble specific parts of the human brain, which include architecture composition and physiology, can provide an alternative system that may lead to breakthroughs in key areas of drug testing and toxicological evaluation. Having reliable and scalable iPSC-derived brain organoid models that can much more accurately predict human drug responses will significantly increase success rate in developing treatments for brain-related disorders.
发现治疗精神和神经疾病的新疗法的道路受到缺乏相关测试平台的严重阻碍。目前，在临床前测试中显示出前景的药物中，约有 0.1%进入了 I 期临床试验，而其中 90%的药物未能获得 FDA 批准。导致这种低成功率的原因之一是传统的二维（2D）细胞培养模型不能准确预测药物在人体中的作用方式。由诱导多能干细胞（iPSC）分化而来的三维（3D）脑类器官类似于人脑的特定部位，包括结构组成和生理学，可以提供一个替代系统，可能在药物测试和毒理学评估的关键领域取得突破。拥有可靠和可扩展的 iPSC 衍生的脑类器官模型，可以更准确地预测人类对药物的反应，这将显著提高开发治疗与大脑相关疾病的治疗方法的成功率。
