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

• ClinicalTrials.gov Identifier: NCT05740761
• Recruitment Status: Recruiting
• First Posted: February 23, 2023
• Last Update Posted: February 23, 2023
• Sponsor: University of Siena
• Information provided by (Responsible Party): Ilaria Meloni, University of Siena

Tracking Information

• First Submitted Date: February 13, 2023
• First Posted Date: February 23, 2023
• Last Update Posted Date: February 23, 2023
• Actual Study Start Date: March 1, 2021
• Actual Primary Completion Date: March 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 13, 2023)

Editing efficiency [ Time Frame: 3 years ]

Percentage of gene editing achieved for each mutation

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: February 13, 2023)

Editing specificity [ Time Frame: 3 years ]

Evaluation of off-targets

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Gene Editing as a Therapeutic Approach for Rett Syndrome
• Official Title: Personalized MECP2 Gene Therapy Using CRISPR/Cas9 Technology Coupled to AAV-mediated Delivery in 3D Cell Culture and KI Mice
• 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.
• 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 Type: Observational
• Study Design: Observational Model: Other; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Patients affected by Rett syndrome with one of the four hotspots mutations in MECP2 gene: p.T158M, p.R255X, p.R168X, p.R306C
• Condition: Rett Syndrome

Intervention

Other: Gene editing in vitro

Testing of gene editing efficiency in vitro in human cellular models derived from patients

• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 13, 2023): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 1, 2024
• Actual Primary Completion Date: March 1, 2022 (Final data collection date for primary outcome measure)

Eligibility 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;

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Rett Syndrome affects almost exclusively females

• Ages: 6 Months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ilaria Meloni, BS.PhD; +390577233259; ilaria.meloni@dbm.unisi.it

• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT05740761
• Other Study ID Numbers: MECPer-3D
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ilaria Meloni, University of Siena
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Siena
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: University of Siena
• Verification Date: January 2023