Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study.
Huiping Li, Shu Liu, Caimei Lin, Yuchao Wu, Xiuping Wu, Yukun Huang, Yajun Wu, Xiubin Tong, Xiu Xu
Molecular therapy. Methods & clinical development March 13, 2025 DOI: 10.1016/j.omtm.2025.101413 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pilot study Open-label Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Girls with classic Rett syndrome aged 5-10 years |
| Intervention | Esketamine |
| Duration | 5 weeks (once per week for 5 weeks) |
| Topics | Esketamine |
| Keywords | N-methyl-d-aspartate receptor antagonist Rett syndrome Efficiency Safety Medical research Neurology treatment Pediatric medicine Rare diseases Drug therapy |
| Citations | 5 |
| Key points | Intravenous esketamine was generally well tolerated and showed minimal improvements in behavioral and motor assessments in three girls with Rett syndrome. |
Abstract
Rett syndrome (RTT) is a severe neurodevelopmental disorder. N-Methyl-d-aspartate receptor (NMDAR) antagonism has shown therapeutic potential in preclinical RTT models. We performed a pilot study to explore whether intravenous esketamine, an NMDAR antagonist, alleviates the symptoms of pediatric RTT. This was a prospective, single-arm, single-site, open-label, early phase 1 pilot study. Three girls with classic RTT aged 5-10 years were enrolled. Esketamine was intravenously administrated once per week for 5 weeks. The efficacy assessments included RTT-related questionnaires and video electroencephalograms (VEEGs). Prespecified adverse events (AEs) were monitored using clinical observations and standard laboratory tests. The treatment with intravenous esketamine was generally well tolerated and safe, with some patients experiencing mild AEs, including self-alleviating nausea, vomiting, and irritability. Three participants showed minimal improvements in their Clinical Global Impression Scale-Improvement, Rett Syndrome Behavior Questionnaire, and Revised Motor Behaviors Assessment Scale scores. However, individual differences were observed in the efficacy measures. VEEGs indicated gradual increases in posterior dominant rhythm peak frequency throughout the intervention. This pilot study highlights the potential of esketamine treatment for improving behavioral dysfunction in patients with RTT. Investigating the appropriate dosage form of esketamine may enhance its beneficial effects in RTT with fewer undesirable features.