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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Rett Syndrome
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Ilaria Meloni, BS.PhD; Phone Number: +390577233259; Email: ilaria.meloni@dbm.unisi.it

Study Locations

• Italy
  • Siena, Italy, 53100
    • Recruiting
    • University of Siena
    • Contact: Ilaria Meloni, BS.PhD; Phone Number: +390577233259; Email: ilaria.meloni@dbm.unisi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• 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

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Editing efficiency	Percentage of gene editing achieved for each mutation	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Editing specificity	Evaluation of off-targets	3 years

Collaborators and Investigators

• Sponsor: University of Siena

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): March 1, 2022
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: February 13, 2023
• First Submitted That Met QC Criteria: February 13, 2023
• First Posted (Estimate): February 23, 2023

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: MECPer-3D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No