ArticleScience translational medicine2012
Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABAB receptors with arbaclofen.
Article in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 246 citations in OpenAlex.
- Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies.Journal of autism and developmental disorders · 2016Pooled it
- Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome.Journal of neurodevelopmental disorders · 2022Trial
- Baclofen as an adjuvant therapy for autism: a randomized, double-blind, placebo-controlled trial.European child & adolescent psychiatry · 2019Trial
- Arbaclofen in Children and Adolescents with Autism Spectrum Disorder: A Randomized, Controlled, Phase 2 Trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- STX209 (arbaclofen) for autism spectrum disorders: an 8-week open-label study.Journal of autism and developmental disorders · 2014Trial
- Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome.Psychopharmacology · 2013Trial
- Article
- How copy number variations shape brain developmental disorders: Unraveling the synaptic puzzle.Psychiatry and clinical neurosciences · 2026Review
- A human electrophysiological signature of Fragile X pathophysiology is shared in V1 of Fmr1Nature communications · 2026Article
- sAPPα Inhibits Neurite Outgrowth in Primary Mouse Neurons via GABA B Receptor Subunit 1a.eNeuro · 2026Article
- Cell-intrinsic mechanisms underlying spontaneous activity in the mouse visual cortical slice: implications for fragile X pathophysiology.Journal of neurophysiology · 2026Article
- GABA-independent activation of GABANature communications · 2025Article
- sAPPα inhibits neurite outgrowth in primary mouse neurons via GABA B Receptor subunit 1a.bioRxiv : the preprint server for biology · 2025Article
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- Elevated somatostatin interneuron long-term potentiation minimally regulates temporoammonic plasticity in a mouse model of Fragile X Syndrome.Frontiers in pharmacology · 2025Article
- A comprehensive review of GABA in autism spectrum disorders: associations, mechanisms, and therapeutic implications.Frontiers in psychiatry · 2025Review
- Developmental hearing loss-induced perceptual deficits are rescued by genetic restoration of cortical inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Curation of causal interactions mediated by genes associated with autism accelerates the understanding of gene-phenotype relationships underlying neurodevelopmental disorders.Molecular psychiatry · 2024Article
- EZH2 inhibition reactivates epigenetically silencedFrontiers in neuroscience · 2024Article
- Understanding copy number variations through their genes: a molecular view on 16p11.2 deletion and duplication syndromes.Frontiers in pharmacology · 2024Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism, results from the transcriptional silencing of FMR1 and loss of the mRNA translational repressor protein fragile X mental retardation protein (FMRP). Patients with FXS exhibit changes in neuronal dendritic spine morphology, a pathology associated with altered synaptic function. Studies in the mouse model of fragile X have shown that loss of FMRP causes excessive synaptic protein synthesis, which results in synaptic dysfunction and altered spine morphology. We tested whether the pharmacologic activation of the γ-aminobutyric acid type B (GABA(B)) receptor could correct or reverse these phenotypes in Fmr1-knockout mice. Basal protein synthesis, which is elevated in the hippocampus of Fmr1-knockout mice, was corrected by the in vitro application of the selective GABA(B) receptor agonist STX209 (arbaclofen, R-baclofen). STX209 also reduced to wild-type values the elevated AMPA receptor internalization in Fmr1-knockout cultured neurons, a known functional consequence of increased protein synthesis. Acute administration of STX209 in vivo, at doses that modify behavior, decreased mRNA translation in the cortex of Fmr1-knockout mice. Finally, the chronic administration of STX209 in juvenile mice corrected the increased spine density in Fmr1-knockout mice without affecting spine density in wild-type mice. Thus, activation of the GABA(B) receptor with STX209 corrected synaptic abnormalities considered central to fragile X pathophysiology, a finding that suggests that STX209 may be a potentially effective therapy to treat the core symptoms of FXS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.