Who may be eligible for the Gene Editing as a Therapeutic Approach for Rett Syndrome trial?

Inclusion Criteria: * Patients -exclusively female- since the pathology is linked to the X chromosome, with a clinical diagnosis of Rett syndrome confirmed at the genetic level by the identification, through NGS analysis, for one of the recurrent mutations (mutational hotspots) in the MECP2 gene object of the study: c. 473C\>T - (p.(T158M)), c.502C\>T (p(R168X)), c.763C\>T (p.(R255X)), c.916C\>T (p.(R306C)); * Age above 6 months; * Availability of parents or legal guardians to provide free and informed consent to participate in the study Exclusion Criteria: * NGS diagnosis with the normal outcome; * Positive NGS diagnosis for mutation in MECP2 but with the presence of a mutation different from those under study. * Unwillingness of parents or legal guardians to provide free and informed consent to participate in the study;

ClinicalTrials.gov record NCT05740761

Gene Editing as a Therapeutic Approach for Rett Syndrome

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

Personalized MECP2 Gene Therapy Using CRISPR/Cas9 Technology Coupled to AAV-mediated Delivery in 3D Cell Culture and KI Mice

About this page. This page shows the study's official ClinicalTrials.gov record ↗, with added help to make it easier to understand. We explain medical terms, highlight key details in plain language, and suggest questions you may want to ask the study team.

The record is periodically copied from ClinicalTrials.gov and may lag behind changes. AI summaries are checked by software, not a clinician.Read moreShow less

The official record is written by the study sponsor and published on ClinicalTrials.gov. It may not always reflect the latest changes. Before making any decisions, please confirm important information with the study team and your own healthcare team.

Where you see "AI summary", AI was used to create a plain-language explanation and software checked it against the source. It has not been reviewed by a clinician, so it may contain mistakes or leave out important details.

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.

Study typeObservationalA study in which researchers do not assign participants to a treatment or other intervention. They observe or measure what happens, which may include study visits, tests, questionnaires or a review of medical records.

Age6 months old and older

SexFemale

LocationItaly

AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This prospective laboratory study evaluates CRISPR/Cas9 gene editing combined with AAV delivery in patient-derived 3D cell cultures and knock-in mice. It focuses on the most common MECP2 mutations found in people with Rett syndrome. The study measures how often editing occurs and whether unintended (off-target) edits happen.

What it is studying. The study is testing CRISPR/Cas9 gene-editing tools delivered by AAV to see if they can edit four recurrent MECP2 mutations and to measure editing efficiency and off-target effects in laboratory and animal models.

What the researchers hope to learn. To validate CRISPR/Cas9 combined with AAV delivery as a method for editing four common MECP2 mutations and to quantify editing efficiency and specificity.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

We designed the project to validate CRISPR/Cas9-based gene editing combined with AAV-based delivery for correction of the most common MECP2 mutations both in vitro and in vivo.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Other: Gene editing in vitro

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

Patients -exclusively female- since the pathology is linked to the X chromosome, with a clinical diagnosis of Rett syndrome confirmed at the genetic level by the identification, through NGS analysis, for one of the recurrent mutations (mutational hotspots) in the MECP2 gene object of the study:
c. 473C>T - (p.(T158M)), c.502C>T (p(R168X)), c.763C>T (p.(R255X)), c.916C>T (p.(R306C));
Age above 6 months;
Availability of parents or legal guardians to provide free and informed consent to participate in the study

Exclusion criteria

NGS diagnosis with the normal outcome;
Positive NGS diagnosis for mutation in MECP2 but with the presence of a mutation different from those under study.
Unwillingness of parents or legal guardians to provide free and informed consent to participate in the study;

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Detailed description from the registry

The project aims to validate CRISPR/Cas9-based gene editing combined with AAV-based delivery for correction of the most common MECP2 mutations both in vitro and in vivo. The laboratory of the principal investigator is an active member of the European Reference Network for rare malformation syndromes and rare intellectual and neurodevelopmental disorders (ERN-ITHACA).

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Participants (via their parents/guardians) will provide genetic test information and patient-derived biological samples or cells for laboratory research. Those samples will be used to create human cellular models for testing CRISPR/Cas9 gene-editing combined with AAV delivery and to measure editing efficiency and off-target effects (outcomes tracked over the study period). Parents or legal guardians must give informed consent for participation.

How the study is structured. A prospective observational laboratory study using patient-derived 3D cell models and knock-in (KI) mice. Researchers will perform gene-editing experiments and record outcomes over time, with primary measurement of editing efficiency and secondary assessment of editing specificity/off-targets (reported over a 3-year timeframe).

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
The listed sites are in Italy. Is any of them reachable for me, and does the study help with travel?
Which of the eligibility criteria would need to be checked with tests before I could join?

More on Rett syndrome

Clinical trials20 trials listed for Rett syndromeEvery trial the registry lists for Rett syndrome, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Rett syndrome researchLatest monthly update: September 2026. Includes: Seizure add-on drug. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start: Mar 1, 2021
Primary completion: Nov 1, 2025 (estimated)
Study completion: Mar 1, 2026 (estimated)
Target enrollment: 40 participants (estimated)
Last updated on registry: Aug 20, 2025
Data verified: Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor: University of Siena
Principal investigator: Ilaria Meloni, Associate professor
University of Siena

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Ilaria Meloni, BS.PhD 📞 +390577233259 ✉ ilaria.meloni@dbm.unisi.it

Participating sites (1)

University of SienaRecruiting
Siena, Siena, 53100 · Italy
- Ilaria Meloni, BS.PhD · +390577233259 · ilaria.meloni@dbm.unisi.it

Terms used on this page · explanations by MedicalUpdates.ai

informed consent: The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
Inclusion Criteria: The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria: The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
principal investigator: The doctor or scientist responsible for running the study at a site or overall.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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