Quantitative Measurement of Phenylalanine Metabolism in Sapropterin-Responsive Hyperphenylalaninemia

沙丙蝶呤反应性高苯丙氨酸血症中苯丙氨酸代谢的定量测量

• 批准号: 10260445
• 负责人: Cary O. Harding
• 金额: $ 12.18万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10260445
• 关键词: Adult; Appearance; Biological; Biological Assay; Biopsy Specimen; Biotechnology; Blood; Breath Tests; Clinical; Clinical Research; Clinical Trials; Cohort Studies; Disease; Dose; Evaluation; Fasting; Future; Gene Transfer; Goals; Hour; Human; Hyperphenylalaninaemias; Individual; Intake; Liver; Measurement; Measures; Methods; Monitor; Oral; Oral Administration; Outcome; Periodicity; Pharmaceutical Preparations; Pharmacologic Substance; Phenylalanine; Phenylalanine Hydroxylase; Phenylalanine Metabolism Pathway; Phenylketonurias; Plasma; Procedures; Production; Protocols documentation; Rare Diseases; Study Subject; Testing; Therapeutic Effect; Time; Treatment Efficacy; Tyrosine; Work; clinical practice; cohort; dietary; experimental study; gene therapy; gene therapy clinical trial; impression; liver biopsy; metabolomics; minimally invasive; novel; oxidation; pre-clinical assessment; recruit; success; therapeutic evaluation; treatment effect; treatment response; treatment trial

5. PROJECT SUMMARY – PROJECT 2 The goal of this project is to validate noninvasive methods of measuring whole body phenylalanine (Phe) metabolism rates that are not confounded by dietary Phe intake in individuals with phenylalanine hydroxylase (PAH) deficiency. Future clinical trials of liver-directed gene therapy for the treatment of PAH deficiency will require the use of such methods to measure treatment efficacy. We propose to evaluate two different methods of measuring Phe metabolism: 1) measurement of 13CO2 enrichment in breath over time following oral administration of 1-13C-L-phenylalanine, and 2) measurement of plasma Phe clearance and plasma tyrosine production following oral unlabeled Phe challenge in a fasting state. These measures will be repeated over time in the same cohort of study subjects with full or partial PAH deficiency in order to assess the sensitivity and test-retest variability of the methods. This project will assess the sensitivity and stability of the proposed testing methods in measuring Phe metabolism non-invasively and prepare a clinical trial ready protocol for future use.

5. 项目总结-项目2