Translational Medicine, BioTherapeutics, Pfizer Inc., South San Francisco, CA 94080, USA.
Biomark Med. 2012 Feb;6(1):119-29. doi: 10.2217/bmm.11.98.
The pharmaceutical industry is increasingly using biomarkers in clinical trials in order to determine if new drug candidates are displaying the expected pharmacological properties and to give early indications if they are showing efficacy or unexpected toxicity. This is especially true for the development of new drug candidates for psychiatric disorders such as schizophrenia and depression, where it is imperative to understand whether the drug is reaching the brain and acting on the target. A particular challenge for biochemical biomarkers used to determine centrally mediated activity is the relative inaccessibility of the brain to direct sampling of cells or tissues. As a result, the use of biomarkers located in the cerebrospinal fluid and in close contact with the interstitial fluid of the brain has risen in prominence. Cerebrospinal fluid biomarkers allow for the analysis of biochemical changes that reflect pharmacological activity or that may be related to the disease. In the area of psychiatric disorders, many studies have utilized biochemical biomarkers in the cerebrospinal fluid for gaining pharmacodynamic or disease modification information. This review summarizes many of these efforts, and identifies challenges and opportunities for utilizing biomarkers for new drug candidates targeting psychiatric disorders.
制药行业越来越多地在临床试验中使用生物标志物，以确定新的候选药物是否表现出预期的药理特性，并在显示疗效或意外毒性时提供早期迹象。对于精神疾病（如精神分裂症和抑郁症）新候选药物的开发尤其如此，因为必须了解药物是否到达大脑并作用于靶标。用于确定中枢介导活性的生化生物标志物的一个特殊挑战是大脑相对难以直接采样细胞或组织。因此，位于脑脊液中并与大脑间质液密切接触的生物标志物的使用日益受到关注。脑脊液生物标志物可用于分析反映药理活性或可能与疾病相关的生化变化。在精神疾病领域，许多研究已经在脑脊液中利用生化生物标志物来获得药效学或疾病修饰信息。本综述总结了其中的许多努力，并确定了利用生物标志物针对精神疾病的新候选药物的挑战和机遇。
