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

基本信息

批准号：
10019407
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
项目类别：
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/10019407
关键词：
Adult Appearance Biological Biological Assay Biopsy Specimen Biotechnology Blood Breath Tests Clinical Clinical Research Clinical Trials Cohort Studies Diet 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 experimental study gene therapy gene therapy clinical trial impression liver biopsy metabolomics minimally invasive novel oxidation pre-clinical recruit success therapeutic evaluation treatment effect treatment response treatment trial

项目摘要

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. 项目摘要——项目 2 该项目的目标是验证测量全身苯丙氨酸 (Phe) 的无创方法苯丙氨酸羟化酶个体的代谢率不受膳食 Phe 摄入量的影响（PAH）缺乏症。未来用于治疗 PAH 缺乏症的肝脏定向基因疗法的临床试验将进行。需要使用此类方法来衡量治疗效果，我们建议评估两种不同的方法。测量 Phe 代谢的方法：1) 口服后随时间推移呼吸中 13CO2 富集的测量 1-13C-L-苯丙氨酸的施用，以及2)血浆Phe清除率和血浆酪氨酸的测量在禁食状态下口服未标记的苯丙氨酸挑战后的生产将重复这些措施。在具有完全或部分 PAH 缺乏的同一队列研究受试者中进行时间评估，以评估敏感性该项目将评估所提议方法的敏感性和稳定性。非侵入性测量 Phe 代谢的测试方法并准备临床试验方案未来使用。