Safety and Efficacy of AAV9. hMCOLN1co For Patients With Mucolipidosis Type IV

Inclusion criteria

• Must be between 1.5 and 8 years of age(inclusive) at the time of signing the informed consent form
• Diagnosed with Mucolipidosis type IV caused by MCOLN1 gene mutations
• The legal guardian and/or the participant(if applicable) has signed the informed consent form
• Meet the criteria for anesthesia and sedation appropriate for their age(as assessed by the investigator)
• Has completed age-appropriate immunizations according to the National Immunization Program Schedule for Children

Exclusion criteria

• Presence of any contraindication to lumbar puncture or intrathecal therapy (e.g., spina bifida, meningitis, coagulation disorders, obstructive spinal internal fixation devices) or presence of a cerebrospinal fluid (CSF) diversion/shunting device
• At screening, severe joint contracture as assessed by the physiotherapist, affecting functional assessment or intrathecal administration
• X-ray examination indicating severe scoliosis (Cobb angle ≥ 50°)
• History of, or planned, scoliosis corrective surgery within 1 year before or after dosing
• Use of invasive respiratory support (e.g., tracheostomy with positive pressure ventilation) or oxygen saturation while awake < 95% (or < 92% at altitudes > 1000 m)
• Requirement for ≥ 12 hours/day of non-invasive respiratory support within 2 weeks prior to dosing
• Dependence on gastric tube feeding with the majority of nutrition taken non-orally, or body weight below the 3rd percentile for age according to World Health Organization (WHO) standards (patients with an existing gastrostomy are not excluded)
• Active viral infection, including human immunodeficiency virus (HIV), hepatitis B, hepatitis C, etc.
• In the investigator's judgment, occurrence of a serious non-respiratory infection (e.g., pyelonephritis, meningitis) within 4 weeks prior to dosing, or presence of other serious comorbid disease
• In the investigator's judgment, severe renal and/or hepatic impairment
• Known history of epilepsy, diabetes, idiopathic hypocalciuria, symptomatic cardiomyopathy, etc.
• In the investigator's judgment, history of bacterial meningitis or central nervous system disease (including tumors), with MRI/computed tomography (CT) indicating abnormalities that may affect lumbar puncture or cerebrospinal fluid circulation
• In the investigator's judgment, allergy to prednisolone or other glucocorticoids and their excipients
• In the investigator's judgment, allergy to gadolinium or gadolinium-containing contrast agents
• Concomitant use of medications for myopathy/neuropathy, antidiabetic drugs, immunosuppressants, plasma exchange, or immunomodulators (e.g., adalimumab), or receipt of immunosuppressive therapy (e.g., glucocorticoids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab, etc.) within 3 months prior to dosing
• Inability to discontinue laxatives or diuretics within 24 hours prior to dosing
• Oral administration of β-receptor agonists within 30 days prior to dosing
• Anti-AAV9 antibody titer > 1:50 (patients may be enrolled if a repeat test after a 2-4-week interval is ≤ 1:50)
• Clinically significant abnormalities in laboratory parameters prior to gene replacement therapy, such as gamma-glutamyl transpeptidase (GGT)/ALT/AST/total bilirubin (TBIL) > 2 × upper limit of normal (ULN), estimated glomerular filtration rate (eGFR) < 60 mL/min, hemoglobin < 8 or > 18 g/dL, white blood cell count > 20,000/cmm, etc.
• Anticipated need for major surgery (e.g., spinal surgery, tracheostomy) during the study period
• Inability to comply with the study protocol or to attend scheduled follow-up visits
• Refusal to sign the informed consent form and/or unwillingness to maintain the confidentiality of the study data.