Novel Spectral Biomarkers for Alzheimer's Disease

摘要。 迫切需要新的疗法来治疗AD患者，但我们没有生物标志物来确定何时开始 我们缺乏方法来预测疾病的发作和治疗的结果。缓慢 向有效疗法的发展将我们带到了一个关键时刻， 发现不再足以确定成功的治疗方法。如果我们要想 改善临床试验的结果或开发更有效的治疗方法。我们建立了一个新的平台 用于治疗AD患者和新的生物标志物以跟踪疗效。该平台是XJB-5-131，一个强大的 电子清除剂，其通过直接靶向线粒体（MT）来发挥其作用，除了其他作用外， 中和氧损伤和炎症。新的生物标志物是细胞的光谱表型。不同 从更传统的端点，我们将使用傅里叶变换红外光谱（FTIR）， 细胞化学的变化。新的生物标记物方法是强大的，因为细胞化学变化， 疾病状态和对药物的反应。傅立叶变换红外光谱是足够敏感的检测疾病状态和药物 方面的影响.这些发现来自于评估XJB-5-131在HD动物模型中的作用。在这一提议中， 我们将把这些方法应用于AD动物模型和人AD成纤维细胞。具有不同突变的动物 将使用FTIR生物标志物测试背景的响应时间和程度。AD成纤维细胞 没有已知致病突变的患者将根据FTIR特征进行分组。我们将测试 相同FTIR类别的患者，即，同样的化学反应，对XJB-5-131也有同样的反应目标是 开发有效的治疗方法和新的生物标志物，以评估何时开始治疗并预测发病 和治疗结果。

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.