MECPer-3D: Gene Editing as a Therapeutic Approach for Rett Syndrome

• Sponsor: University of Siena (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05740761
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Anticipated Duration (Months): 36
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Rett Syndrome	Other: Gene editing in vitro

Detailed Description

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).

Study Design

• Study Type: Observational
• Anticipated Enrollment: 40 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Personalized MECP2 Gene Therapy Using CRISPR/Cas9 Technology Coupled to AAV-mediated Delivery in 3D Cell Culture and KI Mice
• Actual Study Start Date: Mar 1, 2021
• Actual Primary Completion Date: Mar 1, 2022
• Anticipated Study Completion Date: Mar 1, 2024

Outcome Measures

Primary Outcome Measures

1. Editing efficiency [3 years]

   Percentage of gene editing achieved for each mutation

Secondary Outcome Measures

1. Editing specificity [3 years]

   Evaluation of off-targets

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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:

1. 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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Siena	Siena		Italy	53100

Sponsors and Collaborators

• University of Siena

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Ilaria Meloni, Associate professor, University of Siena
• ClinicalTrials.gov Identifier: NCT05740761
• Other Study ID Numbers: MECPer-3D
• First Posted: Feb 23, 2023
• Last Update Posted: Feb 23, 2023
• Last Verified: Jan 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Rett Syndrome; Syndrome

Study Results

No Results Posted as of Feb 23, 2023