First gene therapy trial launches for rare childhood disease MLIV

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Must be between 1.5 and 8 years of age(inclusive) at the time of signing the informed consent form 2. Diagnosed with Mucolipidosis type IV caused by MCOLN1 gene mutations 3. The legal guardian and/or the participant(if applicable) has signed the informed consent form 4. Meet the criteria for anesthesia and sedation appropriate for their age(as assessed by the investigator) 5. Has completed age-appropriate immunizations according to the National Immunization Program Schedule for Children Exclusion Criteria: 1. 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 2. At screening, severe joint contracture as assessed by the physiotherapist, affecting functional assessment or intrathecal administration 3. X-ray examination indicating severe scoliosis (Cobb angle ≥ 50°) 4. History of, or planned, scoliosis corrective surgery within 1 year before or after dosing 5. Use of invasive respiratory support (e.g., tracheostomy with positive pressure ventilation) or oxygen saturation while awake \< 95% (or \< 92% at altitudes \> 1000 m) 6. Requirement for ≥ 12 hours/day of non-invasive respiratory support within 2 weeks prior to dosing 7. 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) 8. Active viral infection, including human immunodeficiency virus (HIV), hepatitis B, hepatitis C, etc. 9. 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 10. In the investigator's judgment, severe renal and/or hepatic impairment 11. Known history of epilepsy, diabetes, idiopathic hypocalciuria, symptomatic cardiomyopathy, etc. 12. 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 13. In the investigator's judgment, allergy to prednisolone or other glucocorticoids and their excipients 14. In the investigator's judgment, allergy to gadolinium or gadolinium-containing contrast agents 15. 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 16. Inability to discontinue laxatives or diuretics within 24 hours prior to dosing 17. Oral administration of β-receptor agonists within 30 days prior to dosing 18. Anti-AAV9 antibody titer \> 1:50 (patients may be enrolled if a repeat test after a 2-4-week interval is ≤ 1:50) 19. 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. 20. Anticipated need for major surgery (e.g., spinal surgery, tracheostomy) during the study period 21. Inability to comply with the study protocol or to attend scheduled follow-up visits 22. Refusal to sign the informed consent form and/or unwillingness to maintain the confidentiality of the study data.