This 5-year study evaluated efficacy and safety of PTC-AADC, a recombinant adeno-associated virus containing cDNA encoding AADC, in children with AADC deficiency.

AADC deficiency is a rare inherited disorder caused by mutations in the DDC gene. Resulting deficiencies of neurotransmitters impede motor development within the first months of life. Current treatments yield little improvement. Gene therapy has been proposed to treat this disorder.

This observational study evaluated data from a single-arm, compassionate-use study enrolling children aged >2 years with AADC deficiency (n=8) receiving intraputaminal PTC-AADC. Primary efficacy end point was proportion achieving key milestones using Peabody Developmental Motor Scale, Second Edition (PDMS-2), vs historical controls (n=82). Secondary end points included changes in PDMS-2, Alberta Infant Motor Scale (AIMS), and Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) scores, and body weight. Pharmacodynamic end points included putaminal ¹⁸F-DOPA uptake on PET. Safety end points included treatment-emergent adverse events (TEAEs) and viral shedding. Mean follow-up was 62.5 months.

 Children with AADC deficiency achieved sustained improvements in motor function after PTC-AADC, with increased putaminal dopamine production. No new safety signals were identified.