From the Department of Neurology, Washington University School of Medicine, St. Louis, MO.
Neurology. 2014 Jul 29;83(5):463-71. doi: 10.1212/WNL.0000000000000652. Epub 2014 Jun 27.
With the emergence of high-throughput discovery platforms, robust preclinical small-animal models, and efficient clinical trial pipelines, it is becoming possible to envision a time when the treatment of human neurologic diseases will become personalized. The emergence of precision medicine will require the identification of subgroups of patients most likely to respond to specific biologically based therapies. This stratification only becomes possible when the determinants that contribute to disease heterogeneity become more fully elucidated. This review discusses the defining factors that underlie disease heterogeneity relevant to the potential for individualized brain tumor (optic pathway glioma) treatments arising in the common single-gene cancer predisposition syndrome, neurofibromatosis type 1 (NF1). In this regard, NF1 is posited as a model genetic condition to establish a workable paradigm for actualizing precision therapeutics for other neurologic disorders.
随着高通量发现平台、强大的临床前小动物模型和高效的临床试验管道的出现，设想有朝一日治疗人类神经疾病将变得个性化成为可能。精准医学的出现将需要确定最有可能对特定基于生物学的治疗有反应的患者亚组。当导致疾病异质性的决定因素得到更充分的阐明时，这种分层才成为可能。这篇综述讨论了与个体化脑肿瘤（视神经通路胶质瘤）治疗的潜力相关的疾病异质性的定义因素，这些治疗源于常见的单基因癌症易感性综合征，即神经纤维瘤病 1 型（NF1）。在这方面，NF1 被认为是一种模型遗传条件，为实现其他神经疾病的精准治疗建立可行的范例。
