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Hyperphenylalaninemia Disorders Consortium of the Rare Disease Clinical Research Network

Award Number: U54HD100982
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $1,523,839 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Child Health and Human Development Extramural Research	001	5	9/6/2023	NON-COMPETING CONTINUATION	$1,523,839
2023	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Child Health and Human Development Extramural Research	000	4	11/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,523,839

Issue Date FY: 2022 ( Subtotal = $1,536,308 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Child Health and Human Development Extramural Research	000	4	9/7/2022	NON-COMPETING CONTINUATION	$1,536,308
														Subtotal = $1,536,308

Issue Date FY: 2021 ( Subtotal = $1,548,508 )
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Child Health and Human Development Extramural Research	002	3	9/3/2021	NON-COMPETING CONTINUATION	$1,548,508
2021	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Child Health and Human Development Extramural Research	000	2	7/20/2021	NON-COMPETING CONTINUATION	$0
2021	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Child Health and Human Development Extramural Research	001	2	8/30/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,548,508

Issue Date FY: 2020 ( Subtotal = $1,567,686 )
2020	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Child Health and Human Development Extramural Research	000	2	9/9/2020	NON-COMPETING CONTINUATION	$1,567,686
														Subtotal = $1,567,686

Issue Date FY: 2019 ( Subtotal = $1,707,037 )
2019	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Child Health and Human Development Extramural Research	000	1	9/16/2019	NEW	$1,707,037
														Subtotal = $1,707,037

Grand Total All Awards = $7,883,378

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Hyperphenylalaninemia Disorders Consortium of the Rare Disease Clinical Research Network

Award Number: U54HD100982

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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