Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study
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...
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050125000087 |
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| author | Huiping Li Shu Liu Caimei Lin Yuchao Wu Xiuping Wu Yukun Huang Yajun Wu Xiubin Tong Xiu Xu |
| author_facet | Huiping Li Shu Liu Caimei Lin Yuchao Wu Xiuping Wu Yukun Huang Yajun Wu Xiubin Tong Xiu Xu |
| author_sort | Huiping Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-82ad43d3fb444d3d9ade9eae54c474e0 |
| institution | Kabale University |
| issn | 2329-0501 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj-art-82ad43d3fb444d3d9ade9eae54c474e02025-02-06T05:11:56ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012025-03-01331101413Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot studyHuiping Li0Shu Liu1Caimei Lin2Yuchao Wu3Xiuping Wu4Yukun Huang5Yajun Wu6Xiubin Tong7Xiu Xu8Department of Child Health Care, Xiamen Children’s Hospital, Children’s Hospital of Fudan University at Xiamen, Xiamen 361006, China; Department of Child Health Care, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China; Corresponding author: Huiping Li, Department of Child Health Care, Xiamen Children’s Hospital, Children’s Hospital of Fudan University at Xiamen, Xiamen 361006, China.Department of Child Health Care, Xiamen Children’s Hospital, Children’s Hospital of Fudan University at Xiamen, Xiamen 361006, ChinaDepartment of Neurology, Xiamen Children’s Hospital, Children’s Hospital of Fudan University at Xiamen, Xiamen 361006, ChinaDepartment of Anesthesiology, Xiamen Children’s Hospital, Children’s Hospital of Fudan University at Xiamen, Xiamen 361006, ChinaPharmacy Department, Xiamen Children’s Hospital, Children’s Hospital of Fudan University at Xiamen, Xiamen 361006, ChinaPediatric Intensive Care Unit, Xiamen Children’s Hospital, Children’s Hospital of Fudan University at Xiamen, Xiamen 361006, ChinaDepartment of Anesthesiology, Xiamen Children’s Hospital, Children’s Hospital of Fudan University at Xiamen, Xiamen 361006, ChinaDepartment of Child Health Care, Xiamen Children’s Hospital, Children’s Hospital of Fudan University at Xiamen, Xiamen 361006, ChinaDepartment of Child Health Care, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China; Corresponding author: Xiu Xu, Department of Child Health Care, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China.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.http://www.sciencedirect.com/science/article/pii/S2329050125000087Rett syndromeesketamineN-methyl-d-aspartate receptor antagonistefficiencysafety |
| spellingShingle | Huiping Li Shu Liu Caimei Lin Yuchao Wu Xiuping Wu Yukun Huang Yajun Wu Xiubin Tong Xiu Xu Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study Molecular Therapy: Methods & Clinical Development Rett syndrome esketamine N-methyl-d-aspartate receptor antagonist efficiency safety |
| title | Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study |
| title_full | Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study |
| title_fullStr | Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study |
| title_full_unstemmed | Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study |
| title_short | Intravenous esketamine in pediatric Rett syndrome: An open-label, early phase 1 pilot study |
| title_sort | intravenous esketamine in pediatric rett syndrome an open label early phase 1 pilot study |
| topic | Rett syndrome esketamine N-methyl-d-aspartate receptor antagonist efficiency safety |
| url | http://www.sciencedirect.com/science/article/pii/S2329050125000087 |
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