Novel diagnostic biomarker reference standards for newborn screening of Mucopolysaccharidoses type I and II.

用于新生儿粘多糖病 I 型和 II 型筛查的新型诊断生物标志物参考标准。

• 批准号: 10757151
• 负责人: Michael H Gelb
• 金额: $ 27.29万
• 依托单位: GELBCHEM, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10757151
• 关键词: Affect; Biological Assay; Biological Markers; Birth; Blood; Businesses; Certification; Chemicals; Clinical; Clinical Research; Dermatan Sulfate; Diagnosis; Diagnostic; Diagnostics Research; Disaccharides; Discrimination; Disease; Dryness; Family; Fibroblasts; Glycosaminoglycans; Goals; Grant; Hand; Heparitin Sulfate; High Prevalence; Hydroxyl Radical; Isotopes; Laboratories; Life; Liquid Chromatography; Lysosomal Storage Diseases; Marketing; Measures; Methodology; Methods; Mucopolysaccharidosis I; Neonatal Screening; Newborn Infant; Notification; Pilot Projects; Publishing; Reagent; Recommendation; Reference Standards; Reference Values; Research; Route; Scientist; Series; Source; Spottings; Standard Preparations; Structure; Technology; Testing; Treatment outcome; United States; Universities; Validation; Work; clinical diagnosis; commercialization; design; diagnostic biomarker; disease diagnosis; enzyme activity; genetic disorder diagnosis; improved; interest; novel; novel diagnostics; research clinical testing; screening; screening panel; screening program; tandem mass spectrometry; therapy development

Project Summary The goal of this project is to design and prepare diagnostic biomarker reference standards for the endogenous glycosaminoglycan (GAG) Mucopolysaccharidosis type I (MPS-I) and type II (MPS- II) biomarkers. MPS-I and MPS-II are lysosomal storage disorders (LSDs) which are listed on the Recommended Uniform Screening Panel (RUSP) in the United States and are included in global Newborn Screening (NBS) programs and Pilot studies currently ongoing. One issue with the first- tier enzyme activity screening is the high prevalence of false positives, which may be eliminated by second-tier biomarker screening. The endogenous GAG biomarker method has been shown in recent studies to provide accurate discrimination of diagnosed newborns from the reference range of healthy newborns and newborns with pseudodeficiencies (for MPS-II). Additionally, by this method unique biomarkers have been identified for each disease, which will aid diagnostic labs in clinical evaluation. Currently, no chemically identical, quantified reference standards (which meets recommendations from FDA guidance on bioanalytical method validation) are available on the market. The GAG disaccharide internal standards prepared within the scope of this project will meet the reference standard recommendations indicated by the FDA, which are not currently met by any other product on the market. As a result, GelbChem will be the first supplier of all materials needed to complete bioanalytical validation of the endogenous GAG biomarker method for MPS-I and MPS-II.

项目概要 该项目的目标是设计和准备诊断生物标志物参考标准 内源性糖胺聚糖 (GAG) I 型 (MPS-I) 和 II 型 (MPS- II) 生物标志物。 MPS-I 和 MPS-II 是溶酶体贮积症 (LSD)，被列入 美国推荐的统一筛查小组 (RUSP) 并被纳入全球 新生儿筛查 (NBS) 计划和试点研究目前正在进行中。第一个问题有一个问题—— 分级酶活性筛查的假阳性率很高，可以消除 通过二级生物标志物筛选。内源性GAG生物标志物方法已被证实 在最近的研究中，可以准确地区分确诊新生儿与参考新生儿 健康新生儿和假性缺陷新生儿的范围（针对 MPS-II）。此外，通过 这种方法已经为每种疾病确定了独特的生物标志物，这将有助于诊断 临床评估实验室。目前，没有化学性质相同的量化参考标准 （符合 FDA 生物分析方法验证指南的建议） 市场上有售。 GAG二糖内标物的制备范围 该项目将满足 FDA 指出的参考标准建议，这些建议是 目前市场上任何其他产品都无法满足这一要求。因此，GelbChem 将成为第一个 完成内源性 GAG 生物分析验证所需的所有材料的供应商 MPS-I 和 MPS-II 的生物标志物方法。