Novel Spectral Biomarkers for Alzheimer's Disease

抽象的。 迫切需要新的疗法来治疗AD患者，但我们没有生物标记物来确定何时开始 而且我们缺乏预测疾病发病时间和治疗结果的方法。慢的 走向有效疗法的运动将我们带到了一个节点，在这个节点上，长期使用药物的方法 发现不再足以识别成功的治疗方法。如果我们要做到这一点，就需要新的方法 改善临床试验的结果或开发更有效的治疗方法。我们已经建立了一个新的平台 用于治疗AD患者和追踪疗效的新型生物标志物。平台为XJB-5-131，功能强大 电子清除剂，通过直接针对线粒体(MT)发挥作用，以及其他作用， 中和氧气损伤和炎症。新的生物标志物是细胞的光谱表型。不同 从更传统的终端，我们将使用傅里叶变换红外光(FTIR)光谱显微镜 跟随细胞化学的变化。新的生物标记物方法是强大的，因为细胞化学在 疾病状态和对药物的反应。FTIR足够灵敏，可以同时检测疾病状态和药物 效果。这些发现源于评估XJB-5-131对HD动物模型的影响。在这份提案中， 我们将把这些方法应用于AD动物模型和人类AD成纤维细胞。具有明显突变的动物 将使用FTIR生物标志物对背景进行测试，以确定他们反应的时机和程度。AD成纤维细胞 如果没有已知的致病突变，将根据FTIR特征进行分组。我们将测试一下 同一FTIR类别，即相同化学成分的患者，对XJB-5-131的反应相同。我们的目标是 开发一种有效的治疗方法和一种新的生物标志物来评估何时开始治疗和预测发病 以及治疗结果。

ABSTRACT. New therapies are urgently needed to treat AD patients, but we have no biomarker to determine when to start treatment and we lack approaches to predict the onset of disease and the outcome of therapeutics. The slow movement towards effective therapeutics brings us to a juncture at which longstanding approaches to drug discovery are no longer sufficient to identify successful therapeutics. New methods are needed if we are to improve the outcome of clinical trials or to develop more effective therapies. We have established a new platform for treating AD patients and new kind of biomarker to follow efficacy. The platform is XJB-5-131, a powerful electron scavenger which exerts its effects by targeting mitochondria (MT) directly and, among other effects, neutralizes oxygen damage and inflammation. The new biomarker is the spectral phenotype of the cell. Different from more conventional endpoints, we will used Fourier transform infrared light (FTIR) spectromicroscopy to follows changes in cell chemistry. The new biomarker method is powerful because cell chemistry changes in the disease state and in in response to drugs. FTIR is sensitive enough to detect both the disease state and drug effects. These findings arose from evaluating the effects of XJB-5-131 in HD animal models. In this proposal, we will apply the methods to AD animal models and in human AD fibroblasts. Animals with distinct mutational backgrounds will be tested for the timing and extent of their response using the FTIR biomarkers. AD fibroblasts with no known disease-causing mutation will be grouped according to the FTIR signature. We will test whether patients in the same FTIR class, i.e., the same chemistry, respond the same way to XJB-5-131. The goal is to develop an effective therapy and a new biomarker to evaluate when to start treatment and to predict the onset and outcome of treatment.