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Updated: May 10, 2026
TMS: Using the Theta-Burst Protocol to Explore Mechanism of Plasticity in Individuals with Fragile X Syndrome and Autism
Published on: December 28, 2010
Gaboxadol increases resting theta and alpha power without affecting evoked responses in fragile X syndrome in a
Lisa A De Stefano1, Hyeonseok Kim2, Craig A Erickson2,3
1Division of Child and Adolescent Psychiatry, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. lisa.destefano@cchmc.org.
Background:
Fragile X syndrome (FXS) lacks FDA-approved treatments despite various small molecules contributing to phenotypic rescue in the FMR1 knockout (KO) mouse model. Translation from the mouse model has been hampered by phenotypic heterogeneity that contributes to participation barriers among participants who are most affected and may be unable to regularly visit the research laboratory. The current study utilized a crossover design to test the acute neural and behavioral effects of a single 10 mg dose of gaboxadol and the reliability of electroencephalography (EEG) and behavioral data collected in participant homes compared to the clinic.
Methods:
Ten adult males with full mutation FXS completed four blinded dosing visits (two placebo, two gaboxadol), with two occurring in-home and two in-lab. Pre- and post-dose assessments included resting high-density EEG, an auditory chirp paradigm, RBANS List Learning, and NIH Toolbox Cognition Battery subtests.
Results:
No serious adverse events were reported. Compared with placebo, gaboxadol increased theta and alpha band power, with no interaction between collection environment (home vs. lab). Additionally, gaboxadol increased the proportion of electrodes with detectable low-frequency peaks and slowed the peak frequency. There were no effects on auditory-evoked measures or NIH Toolbox, with only a marginal effect on RBANS List Learning. An analysis of pre-dose EEG found reliability estimates across testing locations for all tested resting power and behavioral measures that were similar to in-lab reliability estimates found in the literature.
Conclusions:
Single-dose gaboxadol augmented theta and alpha power in FXS during resting EEG, similar to previous findings in the typically developing population and in the FMR1 KO, without normalizing gamma abnormalities, altering auditory-evoked responses, or contributing to behavioral change. These results did not significantly differ between the home and lab settings, supporting the feasibility of in-home data collection for clinical trials in FXS, including those that use complex measures such as EEG as endpoints.
Trial Registration:
clinicaltrials.gov, NCT06334419, Registration Date: March 8, 2024.
Insights
Single-dose gaboxadol increased theta and alpha brainwave activity in Fragile X syndrome (FXS) individuals, showing promise for remote clinical trial data collection. This study did not find significant behavioral changes, highlighting the need for further research into FXS treatments.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Fragile X syndrome (FXS) currently lacks FDA-approved treatments, despite promising results in mouse models.
- Phenotypic heterogeneity in FXS poses challenges for clinical trial participation and data collection.
- This study investigated gaboxadol's effects and the feasibility of in-home data collection for FXS trials.
Purpose of the Study:
- To assess the acute neural and behavioral effects of a single 10 mg dose of gaboxadol in adult males with FXS.
- To evaluate the reliability of electroencephalography (EEG) and behavioral data collected in participant homes versus a clinical setting.
- To explore gaboxadol's potential as a therapeutic agent and in-home data collection as a viable strategy for FXS clinical trials.
Main Methods:
- A crossover design was employed with ten adult males diagnosed with full mutation FXS.
- Participants completed four blinded dosing visits (two placebo, two gaboxadol), alternating between in-home and in-lab settings.
- Assessments included high-density resting EEG, auditory chirp paradigm, RBANS List Learning, and NIH Toolbox Cognition Battery subtests.
Main Results:
- Gaboxadol significantly increased theta and alpha band power in resting EEG, with no difference between home and lab collection.
- The drug increased low-frequency peaks and slowed peak frequency in EEG, but did not affect auditory-evoked responses or cognitive tests.
- Reliability estimates for EEG and behavioral measures were comparable between in-home and in-lab testing.
Conclusions:
- Single-dose gaboxadol augmented specific EEG power bands in FXS, consistent with prior research, but did not yield behavioral improvements.
- The study supports the feasibility of conducting FXS clinical trials using in-home data collection, even with complex measures like EEG.
- Further research is needed to explore gaboxadol's therapeutic potential and optimize remote data acquisition strategies for FXS.
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