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Background <p>Fragile X syndrome (FXS) lacks FDA-approved treatments despite various small molecules contributing to phenotypic rescue in the <i>FMR1</i> 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&#xa0;mg dose of gaboxadol and the reliability of electroencephalography (EEG) and behavioral data collected in participant homes compared to the clinic.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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 <i>FMR1</i> 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.</p> Trial registration <p>clinicaltrials.gov, NCT06334419, Registration Date: March 8, 2024.</p>

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Gaboxadol increases resting theta and alpha power without affecting evoked responses in fragile X syndrome in a home-based setting

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月8日

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  • Lisa A. De Stefano,
  • Hyeonseok Kim,
  • Craig A. Erickson,
  • Lauren M. Schmitt,
  • Kelli C. Dominick,
  • Ernest V. Pedapati,
  • Richard Huckle,
  • Robert Wilson,
  • Walker S. McKinney,
  • Debra L. Reisinger,
  • Meredith N. Nelson,
  • Ashley E. Dapore,
  • Paul S. Horn,
  • Makoto Miyakoshi

摘要

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.