Urine podocyte and podocyte GL3: novel screening tools for phenotype assessment and treatment efficacy in Fabry disease
尿液足细胞和足细胞 GL3:用于法布里病表型评估和治疗效果的新型筛选工具
基本信息
- 批准号:10644824
- 负责人:
- 金额:$ 15.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-19 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AgeAlbuminuriaAlgorithmsAlpha-galactosidaseBiological AssayBiological MarkersBiopsyCRISPR/Cas technologyCalibrationCardiomyopathiesCell LineCell modelCellsCicatrixClassificationClinicalClinical DataComparative StudyComplicationConsumptionCorrelation StudiesDataDatabasesDetectionDevelopmentDiagnosisDiseaseDisease ProgressionEarly DiagnosisElectron MicroscopyEnzymesFabry DiseaseFemaleFlow CytometryGenesGenotypeGlycosphingolipidsGuidelinesIllinoisImageIn VitroInfantInjuryInjury to KidneyInstitutionKidney DiseasesKidney FailureLaboratoriesLinkLysosomal Storage DiseasesMeasurementMeasuresMethodsMicroscopyMinnesotaMissouriModelingMonitorMutationNeonatal ScreeningNeuropathyOnset of illnessOrganPathogenesisPathogenicityPatient CarePatientsPhenotypePlayProceduresProteinuriaProtocols documentationRecommendationResearch PersonnelRoleScreening procedureSeveritiesSignal TransductionSpecimenStandardizationTechniquesTechnologyTennesseeTestingTimeTranslational ResearchTreatment EfficacyUnited States National Institutes of HealthUniversitiesUrineWashingtonX Chromosomecell typeclinically relevantcomputerized data processingdetection assaydisease phenotypedisorder riskenzyme deficiencyenzyme substratefollow-upgastrointestinalglobotriaosylceramideinsightmalemorphometrymortalitynovelorgan injurypodocytepostmitoticpotential biomarkerprognostic significancerecruitscreeningscreening paneltool
项目摘要
Project Summary-Abstract:
Fabry disease is caused by deficiency of a lysosomal enzyme a-galactosidase-A, that leads to accumulation of
the enzyme substrates and mostly globotriaosylceramide (GL3). Since Fabry disease pathogenesis is closely
linked to GL3 accumulation, establishing a diagnosis of Fabry disease requires demonstration of a-
galactosidase-A deficiency and accumulation of GL3 in cells/organs. Newborn screening can identify infants
with a-galactosidase-A deficiency. However, there is no non-invasive assay for detection of GL3 accumulation
in key cells. This is a challenge for deciding who needs treatment and when treatment needs to be started.
Fabry nephropathy is a major complication and the second cause of mortality in patients with Fabry disease.
Podocytes play pivotal role in kidney failure in Fabry patients. Our study will use state-of-the-art imaging flow
cytometry techniques to develop standardized protocols for quantifying podocytes in the urine as an indication
of Fabry nephropathy. In addition, our assay will measure GL3 in urine podocytes. We will develop standard
protocols using a Fabry podocyte cell line that we have developed using CRISPR/Cas9 approach. We will
calibrate our GL3 measurement technique using correlative electron microscopy and unbiased stereology. We
will test our protocols in urines collected from patients with Fabry disease with correlations with urine function
and relevant clinical data. Development of this test will be an important addition to screening Fabry patients for
early detection of disease complication and treatment.
项目摘要-摘要:
法布里病是由溶酶体酶α-半乳糖苷酶-A的缺乏引起的,其导致
酶底物和主要是神经酰胺三己糖苷(GL 3)。由于法布里病的发病机制与
与GL 3积累相关,确定法布里病的诊断需要证明-
半乳糖苷酶-A缺乏和GL 3在细胞/器官中的积累。新生儿筛查可以识别婴儿
缺乏α-半乳糖苷酶然而,没有用于检测GL 3积累的非侵入性测定法
在关键的细胞。这对于决定谁需要治疗以及何时需要开始治疗是一个挑战。
法布里病肾病是法布里病患者的主要并发症和第二大死亡原因。
足细胞在法布里病患者的肾衰竭中起关键作用。我们的研究将使用最先进的成像流程
细胞计数技术,以开发用于定量尿液中足细胞作为指示的标准化方案
法布里病肾病此外,我们的测定将测量尿足细胞中的GL 3。我们将制定标准
使用我们使用CRISPR/Cas9方法开发的法布里足细胞系的方案。我们将
使用相关电子显微镜和无偏体视学校准我们的GL 3测量技术。我们
将在从法布里病患者收集的尿液中测试我们的方案与尿功能的相关性
相关临床数据。这项测试的发展将是一个重要的补充,筛选法布里病患者,
早期发现疾病并发症和治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Behzad Najafian其他文献
Behzad Najafian的其他文献
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{{ truncateString('Behzad Najafian', 18)}}的其他基金
Podocyturia, a Non-Invasive Predictor of Renal Dysfunction in Fabry Nephropathy
足细胞尿,法布里肾病肾功能障碍的非侵入性预测因子
- 批准号:
8934178 - 财政年份:2015
- 资助金额:
$ 15.55万 - 项目类别:
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