title: A randomized, placebo-controlled, double-blind study of sapropterin to treat ADHD symptoms and executive function impairment in children and adults with sapropterin-responsive phenylketonuria.
abstract: Symptoms of attention deficit-hyperactivity disorder (ADHD), particularly inattention, and impairments in executive functioning have been reported in early and continuously treated children, adolescents, and adults with phenylketonuria (PKU). In addition, higher blood phenylalanine (Phe) levels have been correlated with the presence of ADHD symptoms and executive functioning impairment. The placebo-controlled PKU ASCEND study evaluated the effects of sapropterin therapy on PKU-associated symptoms of ADHD and executive and global functioning in individuals who had a therapeutic blood Phe response to sapropterin therapy. The presence of ADHD inattentive symptoms and executive functioning deficits was confirmed in this large cohort of 206 children and adults with PKU, of whom 118 responded to sapropterin therapy. In the 38 individuals with sapropterin-responsive PKU and ADHD symptoms at baseline, sapropterin therapy resulted in a significant improvement in ADHD inattentive symptoms in the first 4 weeks of treatment, and improvements were maintained throughout the 26 weeks of treatment. Sapropterin was well-tolerated with a favorable safety profile. The improvements in ADHD inattentive symptoms and aspects of executive functioning in response to sapropterin therapy noted in a large cohort of individuals with PKU indicate that these symptoms are potentially reversible when blood Phe levels are reduced.
authors.affiliation: The Ann and Robert H. Lurie Children's Hospital and the Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address: BBurton@luriechildrens.org.
authors.forename: B
authors.initials: B
authors.lastname: Burton
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Grant
authors.affiliation: The Hospital for Sick Children and University of Toronto, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Feigenbaum
authors.affiliation: Emory University School of Medicine, Decatur, GA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Singh
authors.affiliation: University of California, San Francisco, San Francisco, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hendren
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Siriwardena
authors.affiliation: Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Phillips
authors.affiliation: University of South Florida and Tampa General Hospital, Tampa, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Sanchez-Valle
authors.affiliation: Boston Children's Hospital, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Waisbren
authors.affiliation: IWK Health Centre Maritime Medical Genetics Services, Halifax, NS, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Gillis
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Prasad
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Merilainen
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Lang
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.affiliation: University of California, San Diego School of Medicine, San Diego, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stahl
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D001708:Biopterins / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D056344:Executive Function / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D010649:Phenylalanine / Q000097:blood*; D010661:Phenylketonurias / Q000150:complications / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin
keywords: Attention deficit–hyperactivity disorder; Mental health; PKU; Phenylketonuria; Sapropterin; Treatment