Novel Metabolic Biomarker for Autism Spectrum Disorder

自闭症谱系障碍的新型代谢生物​​标志物

• 批准号: 8440742
• 负责人: Charles E Schwartz
• 金额: $ 12.16万
• 依托单位: GREENWOOD GENETIC CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-09 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8440742
• 关键词: Affect; Aluminum; Autistic Disorder; Behavior; Behavioral; Biochemical; Biological Assay; Biological Markers; Blinded; Blood; Blood specimen; Cell Line; Cells; Child; Classification; Clinical; Complex; Data; Defect; Diagnosis; Disease; Energy-Generating Resources; Etiology; Frequencies; Future; Generations; Genetic; Genomics; Goals; Human; Individual; Laboratories; Laboratory Diagnosis; Leukocytes; Metabolic; Methods; Microarray Analysis; NADH; Nicotinamide adenine dinucleotide; Output; Patients; Pattern; Phenotype; Physicians; Prevalence; Production; Rest; Sampling; Side; Social Interaction; Staging; Testing; Time; Tryptophan; United States; autism spectrum disorder; clinical Diagnosis; cohort; cost; developmental disease; innovation; lymphoblast; lymphoblastoid cell line; neuropsychiatry; novel; novel strategies; research study; screening; social communication; tool

DESCRIPTION (provided by applicant): Autism Spectrum Disorders (ASDs) affect 1/110 children in the United States, but physicians do not yet have an effective laboratory test which can confirm the clinical diagnosis. This proposal aims to develop a quick and reliable metabolic array to identify individuals with ASD. Using Phenotype Microarray plates obtained from Biolog (Hayward, CA), we have been able to show that Nicotinamide Adenine Dinucleotide, reduced form (NADH) production in the presence of tryptophan as only energy source in lymphoblastoid cells was consistently reduced in 54/56 (96.4%) patients with ASD when compared to 40 controls. The first aim of the proposed project is to validate our preliminary findings using a cohort of 50 additional patients and 50 additional controls employing customized Phenotype Microarray plates. The new plates will allow us to test 12 individuals per plate, using just 160,000 cells per individual. The proposed 100 samples, in addition to the 96 samples from the preliminary study, will give statistical power of 95.6% in a one- sided t-test at significance leve of 0.01. The second aim is to use our assay to evaluate the NADH production in the presence of tryptophan in fresh blood samples. As a first step, we plan to use 6 patients and 6 controls that we have already tested to replicate the results observed in lymphoblastoid cell lines in fresh white cells. This first stage will allow us to determine if we are able to observe the same low levels of NADH production in the presence of tryptophan in leukocytes as was observed in lymphoblasts. Next, we will test fresh blood samples from 12 patients with ASD and 12 controls. To reduce output variability, we will try to start the test at the same time for all the samples, coordinating the sampling of the 24 individuals. Finally, we will test 24 patient and 24 control blood samples from new individuals in a blinded fashion to establish the predictive power of this test in patients with ASD. For this last part of the experiment, we will test each sample as soon as it arrives at our laboratory. We will use a single row of 8 wells on the customized plates for each individual, covering the rest of the plate with aluminum foil, to preserve the other rows for future tests. If our preliminary findings in lymphoblasts are confirmed in leukocytes, we would be able to develop a reliable, easy to perform, inexpensive laboratory test which could provide a diagnosis in about 4-5 days. Such a test could represent the first biochemical screening test for ASDs.

描述(由申请人提供)：自闭症谱系障碍(ASD)在美国影响着1/110的儿童，但医生们还没有有效的实验室测试来确认临床诊断。这项建议旨在开发一种快速可靠的代谢阵列来识别ASD患者。使用从Biolog(Hayward，CA)获得的表型微阵列平板，我们已经能够证明，与40名对照组相比，54/56名ASD患者在色氨酸作为唯一能源的情况下，淋巴母细胞中烟酰胺腺嘌呤二核苷酸(NADH)的生成持续减少。拟议项目的第一个目标是使用50名额外的患者和50名使用定制表型微阵列平板的额外对照来验证我们的初步发现。新的试板将允许我们每个试板测试12个个体，每个个体只使用16万个细胞。建议的100个样本，加上初步研究的96个样本，在0.01的显著水平上进行单侧t检验，统计能力为95.6%。第二个目的是使用我们的方法来评估新鲜血液样本中存在色氨酸的情况下NADH的产生。作为第一步，我们计划使用我们已经测试的6名患者和6名对照来复制在新鲜的淋巴母细胞系中观察到的结果。 白血球。这个第一阶段将使我们能够确定我们是否能够观察到在白细胞中存在色氨酸的情况下，与在淋巴母细胞中观察到的一样低水平的NADH产生。接下来，我们将检测12名ASD患者和12名对照的新鲜血液样本。为了减少输出的可变性，我们将尝试对所有样本同时开始测试，协调对24个个体的采样。最后，我们将以盲法测试24名患者和24名对照新个体的血液样本，以确定这项测试在ASD患者中的预测能力。对于实验的最后部分，我们将在每个样品到达我们实验室时立即进行测试。我们将在每个单独的定制板上使用单行8个孔，用铝箔覆盖板的其余部分，以保存其他行以供将来测试。如果我们在淋巴细胞中的初步发现在白细胞中得到证实，我们将能够开发出一种可靠的、易于操作的、廉价的实验室测试，该测试可以在大约4-5天内提供诊断。这样的测试可能是针对自闭症的第一次生化筛查测试。