Advancing Rett Syndrome Research: Insights into MECP2 Function and Therapeutic Approaches

Rett syndrome (RTT) is a rare neurodevelopmental disorder, first recognized more than sixty years ago by Andreas Rett and brought to international attention in 1983 by Bengt Hagberg and colleagues. RTT is a clinical diagnosis based on established criteria which include a regression following a period of apparently normal development and four requisite clinical criteria: partial or complete loss of spoken language and fine motor capabilities, abnormal and absent gait, and the presence of stereotypic hand movements such as hand -wringing or clapping, finger rubbing, or hand mouthing.

The disorder is predominantly associated with mutations in the MECP2 (methyl-binding-CpG protein 2) gene, occurring principally in females, although males have been identified with a variety of neurological deficits including typical RTT, either due to somatic mosaicism or in association with Klinefelter syndrome (47XXY). The function of MECP2 is well-understood to involve principally neural elements (neurons and glia) and appears to regulate the activation or silencing of many genes critical for proper neural development and maintenance. Multiple animal models have been developed and early studies (2007) revealed that reactivation of a normal gene in a mouse model reversed the disorder’s impact. Several clinical trials have been conducted to-date, and two gene therapy trials are on-going in the US, Canada, the UK, and Australia.

Despite this progress, many questions remain to be answered regarding the overall function of MECP2 and the downstream events leading to this profoundly debilitating disorder. This Research Topic aims to deepen the understanding of MECP2's role in RTT, the biological pathways influenced by its mutation, and the translational implications of these insights for treatment and management. Furthermore, it seeks to evaluate the effects of new therapeutic strategies emerging from ongoing clinical trials and genetic research, providing a hopeful outlook towards significantly improving patient outcomes.

To gather further insights into Rett syndrome, we welcome articles addressing, but not limited to, the following themes:
• Neurological impacts of MECP2 mutations
• Early diagnostic criteria and intervention strategies
• Longitudinal studies on the natural progression of RTT
• Outcome studies related to trofinetide utilization
• Advances in gene therapy and recent outcomes in RTT
• Additional therapeutic strategies: DNA/RNA editing and X-chromosome reactivation
• New insights into MECP2 function

Topic Editor Dr Alan Kenneth Percy is a consultant for Acadia Pharmaceuticals. Dr. Benke has received research funding from GRIN2B Foundation, the International Foundation for CDKL5 Research, International Rett Syndrome Foundation, Loulou Foundation, the National Institutes of Health, Rocky Mountain Rett Association and Simons Foundation; consultancy for Alcyone, AveXis, GRIN Therapeutics, GW Pharmaceuticals, the International Rett Syndrome Foundation, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, and Takeda Pharmaceutical Company Limited; clinical trials with Acadia Pharmaceuticals Inc., GW Pharmaceuticals, Ionis, Marinus Pharmaceuticals, Neurogene, Ovid Therapeutics, and Rett Syndrome Research Trust; all remuneration has been made to his department. Additionally, Dr. Neul has received research funding from the International Rett Syndrome Foundation, Rett Syndrome Research Trust, National Institutes of Health, and the Department of defense; served as site investigator for clinical trials conducted by GW Pharmaceuticals, Neuron, Newron, Acadia Pharmaceuticals, Ionis, Neurogene, and Taysha Gene Therapies; personal consultancy fees from Acadia Pharmaceuticals, GW Pharmaceuticals, Hoffmann-La Roche, Neurogene, and Taysha Gene

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review

Keywords: rett syndrome, MECP2, RTT, pediatric, therapeutic strategies, outcomes

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.