Peptide and Protein Biomarkers for Amyotrophic Lateral Sclerosis (ALS)

肌萎缩侧索硬化症 (ALS) 的肽和蛋白质生物标志物

基本信息

批准号：
8081754
负责人：
ROBERT P BOWSER
金额：
$ 6.48万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2011-09-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8081754
关键词：
Adult Age Alzheimer&apos s Disease Amyotrophic Lateral Sclerosis Antibodies Biological Assay Biological Markers Brain Stem Cerebral cortex Cerebrospinal Fluid Clinical Clinical Trials Collection Data Degenerative Disorder Diagnostic Disease Disease Progression Employee Strikes Enzyme-Linked Immunosorbent Assay Future Gender Generations Goals Health Immunoblotting Individual Inflammation Label Lead Liquid Chromatography Mass Spectrum Analysis Measurement Measures Methodology Methods Molecular Monitor Motor Neurons Multiple Sclerosis Onset of illness Oxidative Stress Pathogenesis Pathologic Patients Peptides Plasma Population Proteins Proteome Proteomics Research Role Sampling Site Spinal Cord Symptoms Testing Time Tissues Validation Vascular System Vesicle base cell type diagnostic accuracy drug efficacy insight multiple reaction monitoring new therapeutic target novel tandem mass spectrometry

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: The molecular mechanisms underlying amyotrophic lateral sclerosis (ALS) are unclear and new research directions and hypotheses are necessary to generate novel therapeutic targets. Our proposal will uncover novel peptide and protein biomarkers for ALS. These studies will lead to new insights into disease mechanisms and potential diagnostic determinants for ALS that can be further explored in future studies.

描述（由申请人提供）：肌萎缩侧索硬化症（ALS）是运动神经元退行性疾病的最常见形式，其特征是脊髓、脑干和大脑皮层中运动神经元的进行性丧失。它可以侵袭任何年龄的成年人，但最常见的是 50 至 55 岁之间。导致这种疾病的分子机制尚不清楚，且 ALS 特异性的生物标志物目前尚不清楚。我们使用基于质谱的蛋白质组学的初步数据从脑脊液 (CSF) 中鉴定了一组蛋白质生物标志物，在临床症状发作时可以高度准确地诊断 ALS。我们建议检查更大的 ALS 组和对照受试者，以进一步验证和识别基于蛋白质的 ALS 生物标志物。该提案的目标是进一步探索 ALS 的 CSF 蛋白质组和对照受试者，以确定 ALS 的肽和/或蛋白质生物标志物。我们将利用基于液相色谱的质谱法对能够将 ALS 与对照受试者区分开来的肽进行大型无偏筛选。然后，我们将在不同的受试者组中验证我们的发现，并生成基于质谱的方法来量化 CSF 和/或血浆中的特定肽，以区分 ALS 和对照受试者。然后，我们将使用这组生物标志物根据疾病发作部位、年龄、性别或疾病进展速度来区分 ALS 患者的亚群。这些研究将产生新的 ALS 生物标志物，可用于未来的 ALS 诊断，并在临床试验中测试其监测疾病进展或药物疗效的能力。公共卫生相关性：肌萎缩侧索硬化症 (ALS) 的分子机制尚不清楚，需要新的研究方向和假设来产生新的治疗靶点。我们的提案将发现 ALS 的新型肽和蛋白质生物标志物。这些研究将对 ALS 的疾病机制和潜在诊断决定因素产生新的见解，可以在未来的研究中进一步探讨。