Effects of STX209 (Arbaclofen) on Neurobehavioral Function in Children and Adults with Fragile X Syndrome: A Randomized, Controlled, Phase 2 Trial
Author(s)
Berry-Kravis, Elizabeth M.
Hessl, David
Rathmell, Barbara
Zarevics, Peter
Cherubini, Maryann
Walton-Bowen, Karen
Mu, Yi
Nguyen, Danh V.
Gonzalez-Heydrich, Joseph
Wang, Paul P.
Date Issued
September 2012
Journal
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Berry-Kravis, E. M., D. Hessl, B. Rathmell, P. Zarevics, M. Cherubini, K. Walton-Bowen, Y. Mu, et al. “Effects of STX209 (Arbaclofen) on Neurobehavioral Function in Children and Adults with Fragile X Syndrome: A Randomized, Controlled, Phase 2 Trial.” Science Translational Medicine 4, no. 152 (September 19, 2012): 152ra127–152ra127.
Version
Author's final manuscript
Abstract
Research on animal models of fragile X syndrome suggests that STX209, a γ-aminobutyric acid type B (GABA[subscript 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[subscript B] agonists have potential to improve social function and behavior in patients with fragile X syndrome.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/scitranslmed.3004214
