In 2 single-arm, open-label clinical studies, children with AADC deficiency received AGIL-AADC (total dose, 1.8x10¹¹ vg) as bilateral, intraputaminal, stereotactic infusions during a single operative session. The primary endpoint was achievement of motor developmental milestones on the Peabody Developmental Motor Scale, Second Edition (PDMS-2; total and single-item subscale scores). Total and subscale scores on the Alberta Infant Motor Scale (AIMS) and Bayley-III also assessed developmental milestones. De novo dopamine production was evaluated with F-DOPA PET imaging. Adverse events (AEs) were recorded. Findings were compared with a natural history cohort of severe AADC patients (N=82) using the Fisher exact test (α=0.05).

Patients aged 21 months to 8.5 years (N=18) received AGIL-AADC. None had full head control or could sit unassisted or stand at baseline. At the time of this analysis, all patients had 2 years of posttreatment data; 8 patients had 5 years of posttreatment data. Clinically meaningful improvements were observed in PDMS-2 total score and single-item motor developmental milestones versus natural history controls. Improvements were observed in AIMS scores and Bayley-III total and cognitive and language subscale scores. All patients demonstrated sustained de novo dopamine production. All AEs were associated with the disease; no new safety signals were observed over 5 years.