Enabling use of blood spot cards for accurate high throughput Fragile X screening

能够使用血点卡进行准确的高通量脆性 X 筛查

基本信息

批准号：
8626306
负责人：
GARY J LATHAM
金额：
$ 101.15万
依托单位：
ASURAGEN, INC.
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-20 至 2016-10-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8626306
关键词：
5&apos Untranslated Regions Address Adoption Affect Age Algorithms Alleles Attention deficit hyperactivity disorder Autistic Disorder Behavior Therapy Behavioral Biological Assay Birth Blood CGG repeat Characteristics Clinical Clinical Research Clinical Trials Cognitive Computer software Cyclic GMP DNA DNA amplification Data Data Analyses Detection Development Diagnosis Diagnostic Diagnostic tests Disease Drops Early Diagnosis Early Intervention Elements Ensure Environment FMR1 FMR1 Gene Female Fragile X Gene Fragile X Syndrome Gene Mutation Genes Genetic Goals Incidence Individual Inherited Intellectual functioning disability Intervention Laboratories Link Longitudinal Studies Marketing Mental Retardation Methods Metric Molecular Neonatal Screening Newborn Infant Paper Parents Patients Pharmacologic Substance Phase Phenotype Population Positioning Attribute Prevalence Process Reagent Reflex action Research Resolution Risk Sampling Severity of illness Small Business Innovation Research Grant Solutions Spottings Syndrome System Technology Testing Therapeutic Translational Research Work clinically relevant commercialization cost cost effective early childhood high throughput screening innovation male manufacturing facility motor disorder mutant novel phase 1 study population based prospective public health relevance reagent standard reproductive screening

项目摘要

DESCRIPTION (provided by applicant): The long term goal of this project is to develop accurate, rapid, high throughput and cost-effective screening for fragile X syndrome (FXS) and related disorders. FXS is the most common known genetic cause of autism and inherited intellectual disability, and affects roughly 1 in 4,000 males and 1 in 6,000 females. The incidence of fragile X carriers is as high as 1 in 130 in females and 1 in 250 in males, and these individuals are at risk for additional disorders that impact childhood early development, including autism. Newborn screening (NBS) for fragile X is timely due to the disease prevalence, lack of a clear phenotype at birth and corresponding "diagnostic odyssey", current and emerging options for early interventions, and impact of associated syndromes. Access to an inexpensive and effective high throughput screening technology, however, has been a key hurdle. To address this technology gap, Asuragen has demonstrated feasibility in phase I studies for a streamlined and automated system for blood card processing and fragile X gene detection that exploits an optimized PCR reagent set. Phase I studies were highly successful, resulting in a technology that can consistently and accurately detect fragile X expansions. In Phase II commercialization, these capabilities will be extended by automating a novel, multiplexed screening assay, developing and integrating an innovative set of controls that ensure reliable data interpretations, establishing an automated algorithm for identifying positives using a workflow that can accommodate thousands of samples per day, and incorporating a confirmation approach that leverages Asuragen's validated AmplideX" product technology. As a result, Asuragen will expand on previously successful fragile X SBIR proposals that have led to multiple cutting-edge products by leveraging a team and environment that is ideally suited to develop, optimize, manufacture, and commercialize the proposed Phase II product. The specific aims of this proposal are: Aim 1: Develop and integrate a set of controls, standards, reagents and QC metrics in an optimized workflow that enables high throughput fragile X NBS from FMR1 normal and mutant blood spots. Aim 2: Establish a screening system that integrates automated assay methods and software that can enable the automated analysis of up to 4000 blood spot samples per day. Aim 3: Validate the system in a retrospective clinical study that includes at least 10,000 newborn blood spot samples, with confirmatory reflex testing of expanded alleles.

描述（由申请人提供）：该项目的长期目标是开发准确、快速、高通量且经济有效的脆性 X 综合征 (FXS) 及相关疾病筛查方法。 FXS 是自闭症和遗传性智力障碍最常见的已知遗传原因，影响大约四千分之一的男性和六千分之一的女性。脆性 X 携带者的女性发病率为 130 分之一，男性为 250 分之一，这些人有患影响儿童早期发育的其他疾病的风险，包括自闭症。由于疾病的流行、出生时缺乏明确的表型和相应的“诊断奥德赛”、当前和新兴的早期干预选择以及相关综合征的影响，新生儿脆性 X 线筛查 (NBS) 是及时的。然而，获得廉价且有效的高通量筛选技术一直是一个关键障碍。为了弥补这一技术差距，Asuragen 在 I 期研究中展示了利用优化的 PCR 试剂组进行血卡处理和脆弱 X 基因检测的简化自动化系统的可行性。第一阶段的研究非常成功，产生了一种能够一致、准确地检测脆弱 X 扩展的技术。在第二阶段商业化中，这些能力将通过自动化新颖的多重筛选测定、开发和集成一套创新的控制来扩展，以确保可靠的数据解释，使用每天可容纳数千个样本的工作流程建立自动算法来识别阳性，并结合利用 Asuragen 经验证的 AmplideX" 产品技术的确认方法。因此，Asuragen 将扩展之前成功的脆弱 X SBIR 提案，这些提案已导致通过利用非常适合开发、优化、制造和商业化拟议的第二阶段产品的团队和环境，该提案的具体目标是：目标 1：开发和集成一套。优化的工作流程中包含质控品、标准品、试剂和 QC 指标，可实现 FMR1 正常和突变血斑的高通量脆弱 X NBS 目标 2：建立一个集成自动化测定方法和软件的筛选系统，可实现多达 100 种的自动化分析。每天 4000 个血斑样本目标 3：在回顾性临床研究中验证系统，其中包括至少 10,000 个新生儿血斑样本，并对扩展的等位基因进行验证性反射测试。