Single-Stage, Open-Label Safety and Efficacy Study of AAV2-hAADC Gene Therapy by MRI-Guided Infusion into Midbrain in Children With AADC Deficiency

What this Trial Is About

Researchers are studying the safety and effectiveness of a gene therapy called AAV2-hAADC delivered directly to specific brain areas in children with aromatic L-amino acid decarboxylase (AADC) deficiency. This condition causes motor problems such as loss of movement and dystonia. The study focuses on safety by monitoring side effects, brain imaging, and lab tests, and also looks at how the therapy affects motor function and symptoms in these children. The treatment involves a single-stage, open-label dose-escalation where AAV2-hAADC is infused into targeted brain regions using MRI guidance. Participants are grouped into cohorts receiving different doses, starting with low doses and increasing based on safety reviews. Doses are delivered bilaterally into the substantia nigra pars compacta and ventral tegmental area. The study includes five cohorts varying by age and dose volume, with careful monitoring between dosing groups. During the study, participants undergo evaluations including motor function assessments, symptom diaries, brain scans like PET and MRI, and lab tests on cerebrospinal fluid. Researchers track adverse events related to surgery and treatment over two years. Additional measures include disability and quality of life assessments. Follow-up continues for two years, and participants may join a long-term study to monitor their safety and clinical status beyond the initial period.

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