Effects of STX209 (Arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: A randomized, controlled, phase 2 trial

Elizabeth M. Berry-Kravis, David R Hessl, Barbara Rathmell, Peter Zarevics, Maryann Cherubini, Karen Walton-Bowen, Yi Mu, Danh V. Nguyen, Joseph Gonzalez-Heydrich, Paul P. Wang, Randall L. Carpenter, Mark F. Bear, Randi J Hagerman

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Abstract

Research on animal models of fragile X syndrome suggests that STX209, a γ-aminobutyric acid type B (GABAB) 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 GABAB agonists have potential to improve social function and behavior in patients with fragile X syndrome.

Original languageEnglish (US)
Article number152ra127
JournalScience Translational Medicine
Volume4
Issue number152
DOIs
StatePublished - Sep 19 2012

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  • Medicine(all)

Cite this

Berry-Kravis, E. M., Hessl, D. R., Rathmell, B., Zarevics, P., Cherubini, M., Walton-Bowen, K., Mu, Y., Nguyen, D. V., Gonzalez-Heydrich, J., Wang, P. P., Carpenter, R. L., Bear, M. F., & Hagerman, R. J. (2012). 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(152), [152ra127]. https://doi.org/10.1126/scitranslmed.3004214