ALS biomarkers in the cerebrospinal fluid

描述(由申请人提供)：识别特定疾病的生物标志物提供了一种更好地诊断疾病状况的手段，并有助于临床试验中药物的设计和测试。肌萎缩侧索硬化症(ALS)的特异性生物标志物仍然未知，从而限制了我们提供更快速的疾病诊断的能力。此外，由于缺乏肌萎缩侧索硬化症特异性生物标志物，有必要在肌萎缩侧索硬化症患者的临床试验中使用诸如肌肉力量指标和呼吸功能测量等临床评估来测试潜在的药物益处。这样的测量可能是识别可能具有有限但积极影响的个别药物的不良结果决定因素，从而极大地限制了我们识别最佳药物组合以最大限度地造福患者的能力。我们建议的研究将从脑脊液中识别ALS特异性生物标记物。我们假设，对ALS患者和对照受试者的脑脊液(CSF)进行蛋白质组学分析将识别与疾病相关的定量和定性蛋白质变化。我们的具体目标是利用基于质谱学的蛋白质组学技术来识别出现在ALS患者中的特定蛋白质生物标记物，从而识别ALS的新生物标记物特征。一组肌萎缩侧索硬化症特异性生物标志物对于早期发现疾病和更有效的临床试验至关重要。我们的初步发现表明，我们有能力识别脑脊液中诊断为ALS的质谱峰。我们已经确定了一个由13个可能的ALS特异性生物标志物组成的小组。我们建议的研究将进一步表征这些假定的生物标记物，并检查ALS在疾病进展过程中蛋白质组生物标记物签名模式的变化。

DESCRIPTION (provided by applicant): The identification of biomarkers specific to a particular disease provides a means to better diagnose the disease condition and aids in the design and testing of drugs in clinical trials. Biomarkers specific to amyotrophic lateral sclerosis (ALS) remain unknown, thus limiting our ability to provide a more rapid disease diagnosis. In addition, the lack of ALS specific biomarkers necessitates the use of clinical assessments such as muscle strength indicators and respiratory function measurements to test potential drug benefits in clinical trials of ALS patients. Such measurements may be poor outcome determinants to identify individual drugs that may have limited but positive affects, thereby greatly limiting our ability to identify the best drug combination for maximal patient benefit. Our proposed study will identify ALS specific biomarkers from the cerebral spinal fluid. We hypothesize that a proteomic analysis of cerebral spinal fluid (CSF) from ALS patients and control subjects will identify quantitative and qualitative disease-associated protein changes. Our specific aim is to utilize mass spectrometry based proteomic techniques to identify specific protein biomarkers that occur in ALS patients, thus identifying a novel biomarker signature for ALS. A panel of ALS specific biomarkers is critical for early disease detection and more efficient clinical trials. Our preliminary findings demonstrate the ability to identify mass spectral peaks in the CSF that are diagnostic for ALS. We have identified a panel of 13 putative ALS specific biomarkers. Our proposed studies will both further characterize these putative biomarkers and examine alterations in the proteomic biomarker signature pattern of ALS during disease progression.