Gene editing to correct common MECP2 mutations in Rett syndrome
Personalized MECP2 Gene Therapy Using CRISPR/Cas9 Technology Coupled to AAV-mediated Delivery in 3D Cell Culture and KI Mice
This project will test CRISPR/Cas9 delivered with AAV to correct common MECP2 mutations in females with Rett syndrome using lab and animal work.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 40 (estimated) |
| Ages | 6 Months and up |
| Sex | Female |
| Sponsor | University of Siena Academic / other |
| Locations | 1 site (Siena, Siena) |
| Trial ID | NCT05740761 on ClinicalTrials.gov |
What this trial studies
The project aims to validate CRISPR/Cas9-based gene editing combined with AAV delivery to correct recurrent MECP2 mutations associated with Rett syndrome. Work includes in vitro experiments and in vivo validation in preclinical models. The research focuses on the most frequent MECP2 hotspot mutations and is conducted by a laboratory that is part of the European Reference Network ERN-ITHACA. The protocol is observational for patient-derived samples and experimental for laboratory and animal phases.
Who should consider this trial
Good fit: Ideal candidates are females aged over 6 months with a genetic diagnosis confirming one of the specified recurrent MECP2 mutations (T158M, R168X, R255X, or R306C) and whose parents or legal guardians can provide informed consent.
Not a fit: Patients with no genetic confirmation, with MECP2 mutations other than the listed hotspots, males, or those unable or unwilling to consent are unlikely to benefit from this project, which is primarily preclinical.
Why it matters
Potential benefit: If successful, the approach could correct the underlying MECP2 genetic defects and potentially restore normal gene function, which might reduce or prevent Rett-related symptoms.
How similar studies have performed: Similar gene-therapy and gene-editing approaches for MECP2 and other neurodevelopmental disorders have shown promising results in preclinical models, but clinical success in humans has not yet been demonstrated and MECP2 editing remains experimental.
Eligibility criteria
Show full inclusion / exclusion criteria
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;
Where this trial is running
Siena, Siena
- University of Siena — Siena, Siena, Italy (Recruiting)
Study contacts
- Study coordinator: Ilaria Meloni, BS.PhD
- Email: ilaria.meloni@dbm.unisi.it
- Phone: +390577233259
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.