Hyperphenylalaninemia Disorders Consortium of the Rare Disease Clinical Research Network

罕见疾病临床研究网络高苯丙氨酸血症疾病联盟

基本信息

  • 批准号:
    10481857
  • 负责人:
  • 金额:
    $ 153.63万
  • 依托单位:
  • 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

项目摘要

1. PROJECT SUMMARY – OVERALL We propose to construct a multicenter collaborative consortium to be part of the Rare Diseases Clinical Research Network (RDCRN) that will be dedicated to clinical research on inborn errors of metabolism causing hyperphenylalaninemia (elevated blood phenylalanine), one of the most common abnormalities detected through newborn screening. Hyperphenylalaninemia may be caused by phenylalanine hydroxylase (PAH) deficiency (also colloquially known as phenylketonuria (PKU)), by disorders of biopterin synthesis and recycling, or by a recently described deficiency of a PAH co-chaperone protein named DNAJC12. Newborn screening and dietary phenylalanine restriction, initiated in the US beginning in the 1960s for PAH deficiency, has been convincingly shown through collaborative study to prevent severe cognitive disability in infants and children, but currently, there are no large longitudinal studies of adolescents or adults with PAH deficiency and no long term follow up data at all on children or adults with biopterin synthesis or recycling defects nor of DNAJC12 deficiency. Clinical experience and many small published case series demonstrate that non-adherence to dietary therapy in adolescence and adulthood is commonplace. Chronically elevated blood phenylalanine is associated with a high incidence of executive dysfunction, anxiety, depression, and with impaired educational and vocational potential. Some adults suffer irreversible white matter damage and motor impairment due to chronically elevated blood phenylalanine. Elevated blood phenylalanine during pregnancy is severely teratogenic leading to the so-called maternal PKU syndrome. Novel therapies that are not strictly dependent upon dietary phenylalanine restriction are highly desired, but the appropriate treatment goals are yet poorly understood. What concentration of blood phenylalanine is necessary to guarantee optimal outcome continues to be debated and other biomarkers that correlate with outcome continue to be sought. The objectives of this project are to comprehensively and longitudinally evaluate the health, neurologic, cognitive, neuropsychiatric, patient-reported, and quality-of-life outcomes in a large cohort of individuals of all ages with PAH deficiency, with biopterin synthesis or recycling disorders, or with DNAJC12 deficiency and to explore correlations between outcomes and blood phenylalanine or other biomarkers. The consortium will also form a network of clinical trial sites prepared to readily participate in the evaluation of novel therapeutic agents designed to treat hyperphenylalaninemia disorders. The results of this study will allow refinement and improvement of current and future therapies for the most common inborn error of metabolism and the rarer conditions associated with hyperphenylalaninemia.
1. 项目总结-整体

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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Cary O. Harding其他文献

Long-term management strategies for pegvaliase use in phenylketonuria: Lessons learned from the phase-3 PRISM open-label extension study
  • DOI:
    10.1016/j.gim.2025.101459
  • 发表时间:
    2025-08-01
  • 期刊:
  • 影响因子:
    6.200
  • 作者:
    Cary O. Harding;Kaleigh Bulloch Whitehall;Joshua Lilienstein;Ogun Sazova;Kristin Lindstrom;Drew G. Levy;Barbara K. Burton
  • 通讯作者:
    Barbara K. Burton
404. Therapeutic Correction of PKU in a Mouse Model by Ectopic Expression of PAH and Its BH4- Cofactor Genes in Skeletal Muscle by a Recombinant Triple-Cistronic AAV2-Based Pseudotype 1 Vector
  • DOI:
    10.1016/j.ymthe.2006.08.467
  • 发表时间:
    2006-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Zhaobing Ding;Cary O. Harding;Alexandre Rebuffat;Lina Elzaouk;JonA. Wolff;Beat Thony
  • 通讯作者:
    Beat Thony
Myoadenylate deaminase deficiency caused by alternative splicing due to a novel intronic mutation in the <em>AMPD1</em> gene
  • DOI:
    10.1016/j.ymgme.2005.06.002
  • 发表时间:
    2005-09-01
  • 期刊:
  • 影响因子:
  • 作者:
    Paul J. Isackson;Heather Bujnicki;Cary O. Harding;Georgirene D. Vladutiu
  • 通讯作者:
    Georgirene D. Vladutiu
219. Persistent Correction of Hyperphenylalaninemia Following Liver-Directed, rAAV2/8-Mediated Gene Therapy for Murine Phenylketonuria (PKU)
  • DOI:
    10.1016/j.ymthe.2006.08.244
  • 发表时间:
    2006-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Cary O. Harding;Melanie B. Gillingham;Elizabeth Daghighi;Andrew Bird;Dwight D. Koeberl
  • 通讯作者:
    Dwight D. Koeberl
Intelligence quotient scores among early-treated phenylketonuria patients: results from a systematic literature review
  • DOI:
    10.1186/s13023-025-03830-0
  • 发表时间:
    2025-06-20
  • 期刊:
  • 影响因子:
    3.500
  • 作者:
    Fiona O’Sullivan;Ioannis Tomazos;Francjan J. van Spronsen;Shelagh M. Szabo;Maanasa Venkataraman;Lavanya Huria;Neil Smith;Lachlan Molony;Kim Ingalls;Kathleen Somera-Molina;Rongrong Zhang;Cary O. Harding
  • 通讯作者:
    Cary O. Harding

Cary O. Harding的其他文献

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{{ truncateString('Cary O. Harding', 18)}}的其他基金

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:
    10701016
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10701013
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:
Hyperphenylalaninemia Disorders Consortium of the Rare Disease Clinical Research Network
罕见疾病临床研究网络高苯丙氨酸血症疾病联盟
  • 批准号:
    10260442
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10260443
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10481858
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:
Hyperphenylalaninemia Disorders Consortium of the Rare Disease Clinical Research Network
罕见疾病临床研究网络高苯丙氨酸血症疾病联盟
  • 批准号:
    10019398
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10019405
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:
Hyperphenylalaninemia Disorders Consortium of the Rare Disease Clinical Research Network
罕见疾病临床研究网络高苯丙氨酸血症疾病联盟
  • 批准号:
    10701011
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:
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:
    10481862
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:
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
  • 财政年份:
    2019
  • 资助金额:
    $ 153.63万
  • 项目类别:

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