Investigators at Washington University will examine the effects of sapropterin (Kuvan) on
brain and cognition in individuals with phenylketonuria (PKU) using neuropsychological and
neuroimaging procedures. Sapropterin is a medication developed by BioMarin Pharmaceutical
Inc. that is approved by the FDA for treatment of patients with PKU to reduce phenylalanine
(Phe) levels. Patients beginning treatment with sapropterin as standard clinical care will be
enrolled in the study. As a first step, patients with PKU will receive baseline
neuropsychological and neuroimaging evaluations 1 day prior to beginning treatment with
sapropterin. Screening for response to sapropterin will occur over 4 weeks. At the end of 4
weeks, response to sapropterin will be reviewed. Patients with a reduction of ≥ 20% in blood
Phe (i.e., responders) will receive follow-up neuropsychological and neuroimaging evaluations
after 6 months of treatment with sapropterin. Patients (both responders and nonresponders)
will receive long-term follow-up neuropsychological and neuroimaging evaluations 3 to 5 years
after initial enrollment in the study.
The focus of neuropsychological testing will be executive abilities, as these abilities are
particularly susceptible to disruption in individuals with PKU. We hypothesize that
improvements in these abilities will occur following treatment with sapropterin. For
neuroimaging assessments, structural magnetic resonance imaging (MRI) will permit evaluation
of changes in the structure and volume of the gray and white matter of the brain, whereas
diffusion tensor imaging (DTI) will permit evaluation of microstructural white matter
integrity.
Details
Lead Sponsor:
Washington University School of Medicine
Collaborators:
BioMarin Pharmaceutical University of Missouri-Columbia