An Open-label, Single Arm, Dose-Escalation Clinical Study to Evaluating the Safety, Tolerability and Preliminary Efficacy of a Single Intracerebroventricular Injection of RB001 for the Treatment of SHANK3-related Phelan-McDermid Syndrome.

Inclusion Criteria:

• Age ≥3 years and <18 years (at the time of signing informed consent), any gender
• Genetic test and clinical confirmed diagnosis of SHANK3-related PMS
• Meets diagnostic criteria for moderate or more severe Autism Spectrum Disorder (ASD)
• Intelligence Quotient (IQ) score <70 or Developmental Quotient (DQ) (excluding gross motor) average score <70
• Willing to provide biological samples required for the study (e.g., blood, urine)
• Consent to hospitalization for intracerebroventricular injection surgery
• The holders of parental authority who are able to understand and willing to comply with study requirements and procedures, voluntarily participating and signing the informed consent

Exclusion Criteria:

A pediatric participant who meets any of the following criteria will be excluded from this study:

• Previous or current participation in other PMS drug clinical trials or other AAV gene therapy clinical studies
• Has known allergic constitution, including allergy or hypersensitivity to prednisone acetate, other glucocorticosteroids, their excipients, or local anesthetics
• Subjects with status epilepticus within 3 months prior to enrollment
• Subjects requiring invasive or non-invasive ventilatory support
• Serum anti-AAV neutralizing antibody titer >1:200
• Significant laboratory abnormalities: alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT) with any value above the upper limit of normal; total bilirubin above the upper limit of normal; creatinine ≥159 μmol/L; hemoglobin (Hb) <80 g/L; prothrombin time (PT) prolonged by ≥3 seconds; activated partial thromboplastin time (APTT) prolonged by ≥10 seconds; fasting blood glucose ≥7.0 mmol/L; glycated hemoglobin (HbA1c) ≥6.5%; platelets (PLT) <100×10^9/L
• Subjects with liver disease or history of heart disease that may pose drug-related risks as assessed by the investigator
• Subjects deemed unsuitable for intracerebroventricular administration or with other special circumstances as assessed by the investigator
• Positive for human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis C antibody, syphilis antibody, active TORCH virus infection, or active Epstein-Barr virus infection
• Concomitant use of any of the following medications within 90 days prior to administration, or planned immunosuppressive treatment within 3 months after starting the trial, except for prophylactic medications specified in the protocol (cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab, etc. )
• Other conditions deemed unsuitable for participation in this study by the investigator