Benaroya Research Institute and Immune Tolerance Network, Seattle, WA
Benaroya Research Institute and Immune Tolerance Network, Seattle, WA.
Diabetes. 2021 Apr;70(4):831-841. doi: 10.2337/db20-1185.
The goal of personalized medicine is to match the right drugs to the right patients at the right time. Personalized medicine has been most successful in cases where there is a clear genetic linkage between a disease and a therapy. This is not the case with type 1 diabetes (T1D), a genetically complex immune-mediated disease of β-cell destruction. Researchers over decades have traced the natural history of disease sufficiently to use autoantibodies as predictive biomarkers for disease risk and to conduct successful clinical trials of disease-modifying therapy. Recent studies, however, have highlighted heterogeneity associated with progression, with nonuniform rate of insulin loss and distinct features of the peri-diagnostic period. Likewise, there is heterogeneity in immune profiles and outcomes in response to therapy. Unexpectedly, from these studies demonstrating perplexing complexity in progression and response to therapy, new biomarker-based principles are emerging for how to achieve personalized therapies for T1D. These include therapy timed to periods of disease activity, use of patient stratification biomarkers to align therapeutic target with disease endotype, pharmacodynamic biomarkers to achieve personalized dosing and appropriate combination therapies, and efficacy biomarkers for "treat-to-target" strategies. These principles provide a template for application of personalized medicine to complex diseases.
个性化医学的目标是在正确的时间为正确的患者匹配正确的药物。在疾病与治疗之间存在明确的遗传关联的情况下，个性化医学最为成功。1 型糖尿病（T1D）并非如此，T1D 是一种遗传复杂的免疫介导的β细胞破坏的自身免疫性疾病。研究人员数十年来一直在追踪疾病的自然史，足以使用自身抗体作为疾病风险的预测生物标志物，并成功地进行疾病修正治疗的临床试验。然而，最近的研究强调了与进展相关的异质性，胰岛素损失的非均匀率和诊断前期间的不同特征。同样，在对治疗的免疫特征和结果方面也存在异质性。出乎意料的是，从这些研究中，人们对进展和对治疗的反应的复杂性感到困惑，新的基于生物标志物的原则正在出现，以实现 T1D 的个性化治疗。这些原则包括针对疾病活动期的治疗时机、使用患者分层生物标志物将治疗目标与疾病内型相匹配、药效学生物标志物以实现个性化给药和适当的联合治疗、以及“达标治疗”策略的疗效生物标志物。这些原则为将个性化医学应用于复杂疾病提供了模板。
