Peptide and Protein Biomarkers for Amyotrophic Lateral Sclerosis (ALS)

总结/摘要 肌萎缩侧索硬化症（ALS）是运动神经元最常见的形式， 退行性疾病，其特征在于运动神经元的进行性丧失， 脊髓、脑干和大脑皮层。它可以袭击任何年龄的成年人， 虽然在50-55岁之间最常见。分子 导致这种疾病的机制尚不清楚，ALS的特异性生物标志物 目前未知。我们的初步数据是基于质谱分析 蛋白质组学从脑脊液（CSF）中鉴定了一组蛋白质生物标志物 在接近临床症状时诊断ALS具有高水平的准确性 发病我们建议检查一个更大的ALS和对照组， 进一步验证和鉴定ALS的基于蛋白质的生物标志物。这个的目标 建议进一步探索ALS和对照组的CSF蛋白质组 以鉴定ALS的肽和/或蛋白质生物标志物。我们将利用液体 在肽的大规模无偏筛选中基于色谱的质谱法 区分ALS和对照组然后，我们将验证我们的发现， 分离受试者组并产生基于质谱的方法， 定量CSF和/或血浆中区分ALS与 控制对象。然后，我们将使用这组生物标志物来区分亚- 根据疾病发作部位、年龄、性别或 疾病进展。这些研究将产生新的ALS生物标志物， 可用于未来的ALS诊断，并测试其监测 临床试验中的疾病进展或药物疗效。

Summary/Abstract Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron degenerative disease and is characterized by a progressive loss of motor neurons in the spinal cord, brain stem and cerebral cortex. It can strike adults of any age, though is most common between the ages of 50-55 years. The molecular mechanisms that cause this disease are unclear and biomarkers specific for ALS are currently unknown. Our preliminary data using mass spectrometry based proteomics identified a panel of protein biomarkers from cerebrospinal fluid (CSF) with a high level of accuracy for diagnosing ALS near the time of clinical symptom onset. We propose to examine a much larger group of ALS and control subjects to further validate and identify protein based biomarkers for ALS. The goals of this proposal are to further explore the CSF proteome of ALS and control subjects to identify peptide and/or protein biomarkers for ALS. We will utilize liquid chromatography based mass spectrometry in a large unbiased screen for peptides that distinguish ALS from control subjects. We will then validate our findings in separate subject groups and generate a mass spectrometry based method to quantify specific peptides within the CSF and/or plasma that distinguish ALS from control subjects. We will then use this panel of biomarkers to distinguish sub- populations of ALS patients based on site of disease onset, age, gender, or rate of disease progression. These studies will generate novel biomarkers for ALS that could be used in future diagnostics for ALS and tested for their ability to monitor disease progression or drug efficacy in clinical trials.