A First-in-Human Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of a Novel CRISPR RNA-editing Therapy in Patients with Mecp2 Duplication Syndrome, a Rare Orphan Disease (HERO)

Inclusion criteria

• Males ≥ 2 and ≤18 years at the time of signing informed consent;
• Genetic test and clinical confirmed diagnosis of MDS;
• Stable pattern of seizures, or has had no seizures while currently receiving medical treatment (including antiepileptics) and physical therapy are stable for at least 2 months before screening;
• Willing to adhere to protocol, including biological samples collection and hospitalization for intracerebroventricular injection surgery;
• Acceptable hematology, clinical chemistry, and urine laboratory parameters.

Exclusion criteria

• MECP2 gene triplication;
• Concurrent genetic syndromes other than MDS;
• Significant brain or cerebellar atrophy, or other significant degenerative changes as shown in cranial MRI at screening;
• Prior or current hypertension, cardiomyopathy, myocardial ischemia or atrial fibrillation and other cardiovascular diseases;
• Prior central nervous system surgery within 6 months before enrolment;
• Systemic use of immunosuppressive drugs within 3 months before enrolment;
• Prior gene therapy or oligonucleotide therapy treatments;
• Any other conditions that would not allow the potential subject to complete follow-up examinations during the study and would, in the opinion of the investigator, make the potential subject unsuitable for the study.