ArticleGenes, brain, and behavior2022
Safety and efficacy of genetic MECP2 supplementation in the R294X mouse model of Rett syndrome.
Article in Genes, brain, and behavior, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 3 of them syntheses that pooled it.
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Who cites it
21 citing papers in PubMed, 3 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Is trofinetide a future treatment for Rett syndrome? A comprehensive systematic review and meta-analysis of randomized controlled trials.BMC medicine · 2024Pooled it
- Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders-Implications for Individuals with Rett Syndrome: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Global prevalence of Rett syndrome: systematic review and meta-analysis.Systematic reviews · 2023Pooled it
- Rett syndrome: MECP2 biology, multisystem pathophysiology, and the evolving therapeutic landscape.European journal of pediatrics · 2026Review
- From Gene to Hope: Rett Syndrome and the Rise of Molecular Therapies.Molecular diagnosis & therapy · 2026Review
- Recent advances in epigenetic therapeutics for Rett syndrome: from mechanisms to clinical trials.Frontiers in behavioral neuroscience · 2026Review
- Potentiation of group III metabotropic glutamate receptors positively affects neurophysiological features in a mouse model of Rett syndrome.The Journal of pharmacology and experimental therapeutics · 2025Article
- MeCP2 gene therapy ameliorates disease phenotype in mouse model for Pitt Hopkins syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Synthetic dosage-compensating miRNA circuits allow precision gene therapy for Rett syndrome.bioRxiv : the preprint server for biology · 2024Article
- Rett Syndrome and the Role of MECP2: Signaling to Clinical Trials.Brain sciences · 2024Review
- An automated respiratory data pipeline for waveform characteristic analysis.The Journal of physiology · 2023Article
- Inhibitory Synaptic Influences on Developmental Motor Disorders.International journal of molecular sciences · 2023Review
- Advanced genetic therapies for the treatment of Rett syndrome: state of the art and future perspectives.Frontiers in neuroscience · 2023Review
- Altered motor learning and coordination in mouse models of autism spectrum disorder.Frontiers in cellular neuroscience · 2023Review
- Exploration of group II metabotropic glutamate receptor modulation in mouse models of Rett syndrome and MECP2 Duplication syndrome.Neuropharmacology · 2022Article
- Safety and efficacy of genetic MECP2 supplementation in the R294X mouse model of Rett syndrome.Genes, brain, and behavior · 2022Article
- Focus on autism and other neurodevelopmental disorders.Genes, brain, and behavior · 2022Article
- Breathing disturbances in Rett syndrome.Handbook of clinical neurology · 2022Review
- Article
- Gene therapy for Rett syndrome.Genes, brain, and behavior · 2022Article
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4 authors at 2 institutions in 1 country.
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Abstract
Rett syndrome is a neurodevelopmental disorder caused predominantly by loss-of-function mutations in MECP2, encoding transcriptional modulator methyl-CpG-binding protein 2 (MeCP2). Although no disease-modifying therapies exist at this time, some proposed therapeutic strategies aim to supplement the mutant allele with a wild-type allele producing typical levels of functional MeCP2, such as gene therapy. Because MECP2 is a dosage-sensitive gene, with both loss and gain of function causing disease, these approaches must achieve a narrow therapeutic window to be both safe and effective. While MeCP2 supplementation rescues RTT-like phenotypes in mouse models, the tolerable threshold of MeCP2 is not clear, particularly for partial loss-of-function mutations. We assessed the safety of genetically supplementing full-length human MeCP2 in the context of the R294X allele, a common partial loss-of-function mutation retaining DNA-binding capacity. We assessed the potential for adverse effects from MeCP2 supplementation of a partial loss-of-function mutant and the potential for dominant negative interactions between mutant and full-length MeCP2. In male hemizygous R294X mice, MeCP2 supplementation rescued RTT-like behavioral phenotypes and did not elicit behavioral evidence of excess MeCP2. In female heterozygous R294X mice, RTT-specific phenotypes were similarly rescued. However, MeCP2 supplementation led to evidence of excess MeCP2 activity in a motor coordination assay, suggesting that the underlying motor circuitry is particularly sensitive to MeCP2 dosage in females. These results show that genetic supplementation of full-length MeCP2 is safe in males and largely so females. However, careful consideration of risk for adverse motor effects may be warranted for girls and women with RTT.
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