ArticleDrug design, development and therapy2026
Low-Dose Sevoflurane Restores Prefrontal Excitatory/Inhibitory Balance and Improves Autism-Like Social Behavior: A Preclinical and Pilot Clinical Study.
Article in Drug design, development and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Medications aimed at modulating excitatory/inhibitory (E/I) balance have shown promise in alleviating the behavioral manifestations of autism spectrum disorder (ASD). We therefore aimed to investigate the potential of low-concentration sevoflurane, a GABA Methods: In the preclinical study, BTBR mice were exposed to 1% sevoflurane for 30 minutes daily, 5 days per week, from postnatal weeks 4 to 6. Behavioral and electrophysiological assessments were performed. In the clinical trial, ASD patients received 1% sevoflurane treatments for 2 hours per session, 3-5 times during the first two weeks, followed by 2-3 sessions per week for a total of 12 weeks. Assessments were conducted at baseline and the 14 Results: Our preclinical results demonstrated that repeated exposure to low-concentration sevoflurane restored E/I balance and improved social interaction and social memory without affecting repetitive behaviors. Accordingly, an open-label and single-arm clinical trial enrolled 20 ASD patients in Guangzhou Women and Children's Medical Center. Significant reduction in CARS score of 4.7 points was observed between baseline and the end of treatment, which is both statistically and clinically significant. Additionally, 61% of ASD children demonstrated a positive response as measured by the CGI-I scale. Furthermore, analysis of secondary outcomes revealed that sevoflurane treatment primarily improved social impairments in ASD patients. Importantly, no significant safety concerns were observed during the one-year follow-up. Conclusion: Low-concentration sevoflurane shows promise as a novel therapeutic strategy for improving social deficits in ASD by modulating E/I balance. Trial Registration: Chinese Clinical trial Number: ChiCTR1900027459.
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