AAV9-ASAH1 intracisterna magna Gene Therapy (GNT0009) in Patients with Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy (SMA - PME)

Prior treatment

• Concomitant use of strong CYP3A4 and/or P-glycoprotein (P-gp) inducers or inhibitors
• Presence of any permanent or non-MRI–compatible implants or devices (e.g., metal braces) that preclude safe MRI assessment

Other illness

• Diagnosis of Farber disease
• Positive serology consistent with human immunodeficiency virus (HIV) infection or evidence of active hepatitis B or hepatitis C infection
• Severely impaired pulmonary function (e.g., FVC <30% predicted) and/or respiratory insufficiency requiring either of the following: (a) non-invasive ventilation for >16 hours per day, or (b) invasive mechanical ventilation via tracheostomy
• Coagulation disorders or clinically significant abnormalities in coagulation parameters that increase the risk of bleeding associated with ICM administration

Lab values

• Presence of a severe concomitant medical condition or clinically significant abnormal laboratory / imaging findings that, in the opinion of the investigator, may interfere with the course of SMA-PME or place the participant at increased risk of severe complications

Other

• Severe intellectual disability (e.g., intellectual quotient [IQ] < 50)
• Gross Motor Function Classification in Metachromatic Leukodystrophy (GMFC-MLD) score of 6 (loss of any locomotion as well as loss of any head and trunk control).
• Hepatic dysfunction Grade ≥3 as defined by CTCAE criteria
• History or evidence of increased intracranial pressure, hydrocephalus, or need for CSF diversion

• Male or female participants
• Documented genetically SMA-PME diagnosis
• Up-to-date immunization status according to the French national vaccination schedule (2025), including recommended vaccines for age and/or risk groups, notably: hepatitis B, measles-mumps-rubella (MMR), varicella*, hepatitis A (in at-risk populations), Neisseria meningitidis (ACWY + B), Streptococcus pneumoniae, seasonal influenza, SARS-CoV-2, and respiratory syncytial virus (RSV) where indicated
• Ability of the participant and/or legal representatives to confirm the adherence to the clinical trial visit schedule and all protocol requirements
• Effective contraception