Safety and Effectiveness of MRI-Guided AAV2-hAADC Gene Therapy in Children with AADC Deficiency

What this Trial Is About

Researchers are evaluating the safety and effectiveness of AAV2-hAADC gene therapy delivered directly into specific brain regions in children with aromatic L-amino acid decarboxylase AADC deficiency. This condition causes severe motor function loss and dystonic movements. The study is designed as a Phase 1, open-label, dose-escalation trial to determine the appropriate dose for future studies and to assess safety and clinical outcomes. Participants will receive AAV2-hAADC through an MRI-guided infusion into the substantia nigra pars compacta and ventral tegmental area of the midbrain. The study involves multiple cohorts receiving increasing doses, starting with a low dose in Cohort 1 and higher doses in subsequent cohorts. Infusions are delivered bilaterally at specific brain sites, with dosing intervals and volumes adjusted based on age and safety monitoring. The treatment phase includes follow-up assessments up to two years post-surgery. Throughout the study, participants will be closely monitored for adverse events related to surgery and gene therapy, with brain imaging and laboratory tests to evaluate safety. Clinical responses will be assessed using measures of motor function, symptom diaries, and various developmental and quality of life scales. Follow-up includes cerebrospinal fluid neurotransmitter analysis and PET imaging to assess biological activity. Participants may join a long-term follow-up study to monitor ongoing safety and clinical status.

A Single-Stage, Adaptive, Open-label, Dose Escalation Safety and Efficacy Study of AADC Deficiency in Pediatric Patients