title: Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial.
abstract: Research on animal models of fragile X syndrome suggests that STX209, a γ-aminobutyric acid type B (GABA(B)) agonist, might improve neurobehavioral function in affected patients. We evaluated whether STX209 improves behavioral symptoms of fragile X syndrome in a randomized, double-blind, placebo-controlled crossover study in 63 subjects (55 male), ages 6 to 39 years, with a full mutation in the FMR1 gene (>200 CGG triplet repeats). We found no difference from placebo on the primary endpoint, the Aberrant Behavior Checklist-Irritability (ABC-I) subscale. In the other analyses specified in the protocol, improvement was seen on the visual analog scale ratings of parent-nominated problem behaviors, with positive trends on multiple global measures. Post hoc analysis with the ABC-Social Avoidance scale, a newly validated scale for the assessment of fragile X syndrome, showed a significant beneficial treatment effect in the full study population. A post hoc subgroup of 27 subjects with more severe social impairment showed improvements on the Vineland II-Socialization raw score, on the ABC-Social Avoidance scale, and on all global measures. STX209 was well tolerated, with 8% incidences of sedation and of headache as the most frequent side effects. In this exploratory study, STX209 did not show a benefit on irritability in fragile X syndrome. Nonetheless, our results suggest that GABA(B) agonists have potential to improve social function and behavior in patients with fragile X syndrome.
authors.affiliation: Department of Pediatrics, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Berry-Kravis
authors.forename: David
authors.initials: D
authors.lastname: Hessl
authors.forename: Barbara
authors.initials: B
authors.lastname: Rathmell
authors.forename: Peter
authors.initials: P
authors.lastname: Zarevics
authors.forename: Maryann
authors.initials: M
authors.lastname: Cherubini
authors.forename: Karen
authors.initials: K
authors.lastname: Walton-Bowen
authors.forename: Yi
authors.initials: Y
authors.lastname: Mu
authors.forename: Danh V
authors.initials: DV
authors.lastname: Nguyen
authors.forename: Joseph
authors.initials: J
authors.lastname: Gonzalez-Heydrich
authors.forename: Paul P
authors.initials: PP
authors.lastname: Wang
authors.forename: Randall L
authors.initials: RL
authors.lastname: Carpenter
authors.forename: Mark F
authors.initials: MF
authors.lastname: Bear
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
mesh_terms: D000293:Adolescent; D000328:Adult; D001418:Baclofen / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D001519:Behavior / Q000187:drug effects*; D002648:Child; D005260:Female; D005600:Fragile X Syndrome / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009420:Nervous System / Q000187:drug effects* / Q000473:pathology*; D009483:Neuropsychological Tests; D015203:Reproducibility of Results; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001418:Baclofen