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.

项目摘要 该项目的目标是设计和准备诊断生物标记物的参考标准 内源性糖胺聚糖(GAG)粘多糖病I型(MPS-I)和II型(MPS-I) Ii)生物标志物。MPS-I和MPS-II是溶酶体储存障碍(LSD)，列于 美国推荐的统一筛查小组(RUSP)，并包括在全球 目前正在进行的新生儿筛查(NBS)方案和试点研究。第一个问题是- 层酶活性筛查是假阳性的高发，有可能被消除 经二级生物标志物筛选。内源性Gag生物标记物方法已被证明 在最近的研究中提供了准确区分被诊断的新生儿的参考 健康新生儿和假性缺乏症新生儿的范围(MPS-II)。此外，由 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 临床评估中的实验室。目前，没有化学上相同的、量化的参考标准 (符合FDA关于生物分析方法验证的指南建议) 在市场上有售。二糖内标物的制备范围 该项目将符合FDA指出的参考标准建议，这些建议包括 目前市场上任何其他产品都无法与之相提并论。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。