Evaluation of Behavior, Executive Function, Neurotransmitter Function and Genomic Expression Kuvan Nonresponders
Status:
Completed
Trial end date:
2013-12-01
Target enrollment:
Participant gender:
Summary
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.