Sharlow Elizabeth R, Koseoglu Mehmet Murat, Bloom George S, Lazo John S
Department of Pharmacology, University of Virginia, Charlottesville, Virginia.
Fiske Drug Discovery Laboratory, University of Virginia, Charlottesville, Virginia.
Assay Drug Dev Technol. 2020 Feb/Mar;18(2):97-103. doi: 10.1089/adt.2019.914. Epub 2019 May 16.
Neurological diseases comprise more than a thousand ailments that adversely affect the brain and nervous system. When grouped together, these neurological conditions impact an estimated 100 million individuals in the United States and up to a billion people worldwide, making drug discovery efforts imperative. However, recent research and development efforts for these neurological diseases, including Alzheimer's disease and amyotrophic lateral sclerosis, have been exceedingly disappointing and typify the challenges associated with translating and cell-based discoveries to successful preclinical models and subsequent human clinical trials. Our viewpoint is that neuronal progenitor cells and neurons derived from inducible pluripotent stem cells afford an innovative translational bridge, with higher pathological relevancy than previous cellular models. We outline some of the opportunities and challenges associated with their evolving usage in drug discovery and development.
神经疾病包含一千多种对大脑和神经系统产生不利影响的病症。这些神经病症加在一起，估计影响着美国1亿人以及全球多达10亿人，因此药物研发工作势在必行。然而，最近针对这些神经疾病（包括阿尔茨海默病和肌萎缩侧索硬化症）的研发工作极其令人失望，凸显了将基于细胞的发现转化为成功的临床前模型以及后续人体临床试验所面临的挑战。我们的观点是，源自诱导多能干细胞的神经祖细胞和神经元提供了一座创新的转化桥梁，其病理相关性比以往的细胞模型更高。我们概述了在药物发现和开发中不断演变地使用它们所涉及的一些机遇和挑战。
