F.M. Kirby Neurobiology, Boston Children's Hospital, and Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Sci Transl Med. 2021 Nov 10;13(619):eabj9837. doi: 10.1126/scitranslmed.abj9837.
Despite substantial efforts dedicated to the development of new, nonaddictive analgesics, success in treating pain has been limited. Clinically available analgesic agents generally lack efficacy and may have undesirable side effects. Traditional target-based drug discovery efforts that generate compounds with selectivity for single targets have a high rate of attrition because of their poor clinical efficacy. Here, we examine the challenges associated with the current analgesic drug discovery model and review evidence in favor of stem cell–derived neuronal-based screening approaches for the identification of analgesic targets and compounds for treating diverse forms of acute and chronic pain.
尽管人们为开发新型、非成瘾性的镇痛药付出了巨大努力,但在治疗疼痛方面的成效却有限。临床上可用的镇痛剂通常疗效不足,而且可能具有不良的副作用。传统的基于靶点的药物发现方法旨在生成对单一靶点具有选择性的化合物,但由于其临床疗效不佳,导致其淘汰率很高。在这里,我们研究了当前镇痛药物发现模型所面临的挑战,并回顾了支持基于干细胞衍生神经元的筛选方法的证据,该方法可用于鉴定治疗各种急性和慢性疼痛的镇痛靶点和化合物。