We report interim findings from a phase 2 study on gene therapy with PTC-AADC.

Eight children underwent bilateral intraputaminal injection of PTC-AADC (1.8 × 10¹¹ vg for age ≥3 years and 2.4 × 10¹¹ vg for <3 years). Primary efficacy end point was proportion achieving key milestones using Peabody Developmental Motor Scale, Second Edition (PDMS-2). Secondary end points included changes in PDMS-2, Alberta Infant Motor Scale (AIMS), Bayley-III, 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 11.5 months.

Patients received doses of 1.8 × 10¹¹ vg (n=3; mean age, 55.0 months) or 2.4 × 10¹¹ vg (n=5; 24.8 months). Baseline PDMS-2 and AIMS total scores were low. All patients achieved clinically meaningful gains in motor function as measured by PDMS-2, with 50% of patients achieving full head control by month 12 after treatment. Increases from baseline in PDMS-2, AIMS, and Bayley-III total scores at 1 year were statistically significant (P<0.0001, P≤0.0016, and P≤0.0004, respectively, both doses). Mean body weight increased from baseline to year 1 in both groups. The number of patients with hypotonia, oculogyric crises, and limb dystonia decreased during the first year. No viral shedding was detected. No differences were observed in safety profiles for the doses. All patients experienced ≥1 TEAE, most of mild intensity; none were definitely related to treatment. Mild dyskinesia episodes were considered possibly related to therapy. Of 21 serious AEs, all resolved and were considered unlikely to be related to study treatment.