Evaluation of Behavior, Executive Function, Neurotransmitter Function and Genomic Expression in PKU "Nonresponders" to Kuvan® (Sapropterin Dihydrochloride)

183590-1

This observational study seeks to establish evidence: 1. that physiologic changes, unrelated to effect on the Phenylalanine Hydroxylase (PAH) enzyme, occur in Phenylketonuria (PKU) patients who are treated with sapropterin (Kuvan®) therapy, 2. that these changes may be caused by enhanced neurotransmitter synthesis in the brain or an upregulation of gene expression (increasing the ability of genes to produce functional enzymes), 3. and that beneficial changes in behavior and cognition, especially executive functioning skills may result. The objective of this study is to correlate any change in behavior and executive function skills of PKU patients who are non-responsive to sapropterin effect on the PAH enzyme, as defined by lowered blood PHE levels, with urine neurotransmitter levels and broad gene expression prior to and after sapropterin administration. Expected outcomes would include evidence of sapropterin effects on upregulation of enzymes other than PAH that control neurotransmitter synthesis, and any resulting correlation with behavioral and cognitive changes. The investigators hope this study will inform further detailed investigations into the biochemical and molecular actions of sapropterin (Kuvan®) that lead to increased understanding of possible treatment effects beyond a lowered blood PHE response.

2011-01-01

2013-12-01

2013-12-01

Completed

21

Inclusion Criteria: * established Hayward Genetics Center patients: * confirmed diagnosis of PKU, * aged 2-21 years, * not responsive to sapropterin with decreased blood PHE levels Subsequent to the start of the study inclusion criteria were amended: the upper limit of age was omitted, and a limited number of patients who were naive to sapropterin were recruited. Exclusion Criteria: * pregnancy * preexisting cognitive disorder or concurrent disease that would interfere with participation, * documented equal to or greater than 20% decrease in blood PHE levels as a response to sapropterin administration, * receiving neurotransmitter supplementation or medication for attention deficit hyperactivity disorder (ADHD), * received sapropterin therapy in the 2 months prior to the study

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2023-08-14