Gene therapy for Rett syndrome using AAV-MECP2

Study on the Safety, Tolerability, and Preliminary Efficacy of Single Intrathecal Injection of AAV-MECP2 in the Treatment of Rett Syndrome

This study is testing a new gene therapy for girls aged 4-10 with Rett syndrome to see if it can safely improve their symptoms.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 4 Years to 10 Years
• Sex: Female
• Sponsor: Guangzhou Women and Children's Medical Center (Academic / other)
• Drugs / interventions: rituximab, methotrexate, cyclophosphamide, prednisone
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06856759 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety, tolerability, and preliminary efficacy of a single intrathecal injection of AAV-MECP2 in female patients aged 4-10 years diagnosed with Rett syndrome. The study aims to explore two target doses of the gene therapy product developed by Professor Qiu Zilong, which has shown promise in animal models. Participants will undergo gene testing to confirm functional loss mutations in the MECP2 gene and will be monitored for any adverse effects and potential improvements in symptoms.

Who should consider this trial

Good fit: Ideal candidates are female patients aged 4-10 years with confirmed MECP2 gene mutations and a diagnosis of Rett syndrome.

Not a fit: Patients with neurodevelopmental disorders unrelated to MECP2 gene mutations will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel therapeutic option for improving the quality of life in patients with Rett syndrome.

How similar studies have performed: While gene therapy has shown success in other neuromuscular diseases, this specific approach for Rett syndrome is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. 4-10 years old (at the time of signing the informed consent form), female, who meets the typical RTT diagnosis criteria in 2010.
2. Gene testing confirms functional loss mutations in the MECP2 gene.
3. Complete all Class I vaccination required by the national regulations before the age of enrollment, and the final dose of vaccination must be completed at least 42 days before enrollment.
4. Participate in this study with the informed consent of the guardian, understand the risks of intrathecal injection procedures, and agree to collect blood, urine, and cerebrospinal fluid biological samples required for the experiment, as well as receive necessary blood or blood product treatment or other necessary medical treatment if necessary for the condition.

Exclusion Criteria:

1. Suffering from neurodevelopmental disorders other than MECP2 gene functional loss mutations, or pathogenic gene mutations other than MECP2 gene functional loss mutations discovered by whole exome sequencing.
2. Abnormal neurological function caused by traumatic brain injury or suffocation and hypoxia.
3. Through MRI scan, brain tumors or intracranial space-occupying lesions are detected.
4. Comprehensive abnormal psychomotor development has occurred within 6 months after birth.
5. Diagnosed as atypical RTT.
6. Has MECP2 gene mutation, but clinical diagnosis does not match RTT.
7. Need invasive respiratory support.
8. There are contraindications for lumbar puncture or intrathecal injection, including high cerebrospinal fluid pressure, obvious skin infection at the puncture site, trauma, epidural abscess, severe spinal lesions, deformities, spinal cord compression, bleeding tendency (bleeding tendency caused by the use of heparin, warfarin, etc.
9. Have experienced status epilepticus (\> 30 minutes) or recurrent unstable seizure control (\> 2 generalized seizures per week) in the past 3 months.
10. In addition to RTT, there are other unstable systemic diseases, including active bacteria, fungi, or HIV, hepatitis A, hepatitis B infection.
11. There are significant laboratory indicators with abnormalities: any detection value of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT), alkaline phosphatase (ALP) is ≥ 2 times the upper limit of normal (ULN).
12. Total bilirubin ≥ 1.5 × ULN.
13. Creatinine ≥ 159 μ mol/L.
14. Hemoglobin (Hb) \< 80 g/L.
15. Prothrombin time (PT) prolonged by ≥ 3 seconds.
16. Prolonged activated partial thromboplastin time (APTT) by ≥ 10 seconds.
17. Fasting blood glucose ≥ 7.0 mmol/L.
18. HbA1c ≥ 6.5%.
19. Platelet values are outside the range of 100-300 ×10\^9/L.
20. Serum anti AAV neutralizing antibody titer \> 1:50 (ELISA immunoassay).
21. Systemic use of immunosuppressive drugs (cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immune globulin, and rituximab) other than protocol-specified prophylaxis within 3 months prior to enrollment.
22. Previously received gene therapy.
23. Plan to make changes in clinical medication during this clinical trial, participate in other clinical trials, or have received other investigational drug treatments within 30 days or 5 half lives (whichever is longer) before enrollment.
24. Known allergy to investigational drug.
25. Any condition that, in the opinion of the Investigator, patients are not appropriate to participate in the study.

Where this trial is running

Guangzhou, Guangdong

• Guangzhou Women and Children's Medical Center — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Jingqi Zhang, MSc

Conditions Rett Syndrome; Rett syndrome; AAV-MECP2; Single intrathecal injection; Safety; Tolerability; Preliminary efficacy