约翰霍普金斯医学院的研究人员利用患者细胞培育的微型脑组织（类器官），成功建立了一种预测不同阿尔茨海默病患者对药物反应差异的模型[1]。该研究在患者衍生的类器官中观察到抗抑郁药物艾司西酞普兰草酸盐的分化响应存在个体差异[1]。
研究团队发现，脑类器官分泌的细胞外囊泡中含有特定蛋白质标志物，其中RAB3A、NSF和ATCAY蛋白在阿尔茨海默病组织中的水平较低[1]。这些疾病相关蛋白可能成为新的诊断生物标志物，为开发更加精准的个性化治疗方案提供科学依据[1]。
该研究包括代表数百名个别患者和健康参与者的类器官样本，被认为是迄今为止阿尔茨海默病领域规模最大的脑类器官研究[1]。鉴于该疾病在美国影响超过700万人的现状，这一发现具有重要的临床应用前景[1]。
研究已发表于《阿尔茨海默病与痴呆症：美国阿尔茨海默病协会杂志》，并获得美国国立卫生研究院的资助[1]。
Researchers at Johns Hopkins School of Medicine have developed a novel approach to predicting how individual Alzheimer's disease patients will respond to specific medications using lab-grown brain tissue derived from patient cells.[1] The team cultured miniature brain organoids from patient-derived cells and discovered that these models can identify variations in patient responses to antidepressant drugs, particularly selective serotonin reuptake inhibitors such as escitalopram oxalate.[1]
The research identified disease-associated proteins within extracellular vesicles—small particles released by the brain organoids—that could serve as new diagnostic biomarkers for more personalized treatment approaches.[1] Specifically, the team found that levels of the proteins RAB3A, NSF, and ATCAY were lower in extracellular vesicles from Alzheimer's disease tissue compared to healthy samples.[1] The study examined hundreds of organoids representing individual patients and healthy participants, making it one of the largest brain organoid studies conducted in Alzheimer's disease research to date.[1]
With Alzheimer's disease affecting more than seven million people in the United States,[1] these findings suggest that patient-derived organoid models may enable clinicians to predict drug efficacy before treatment begins. The research was partially supported by the National Institutes of Health and has been published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association.[1]