Improved Motor Function in Children With Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency Treated With Eladocagene Exuparvovec (PTC-AADC): Compassionate Use Study
Paul Wuh-Liang Hwu1, Yin-Hsiu Chien1, Ni-Chung Lee1, Sheng-Hong Tseng1, Mark Pykett2, Chun-Hwei Tai1
1National Taiwan University Hospital, 2PTC Therapeutics, Inc
Objective:

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.

Background:

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.

Design/Methods:

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.

Results:
No enrolled patients had achieved any motor milestones at baseline. Five years after treatment, 4/8 patients exhibited full head control and could sit unassisted (P=0.0002 vs control); 2/8 stood with support (P=0.045 vs control). Mean PDMS-2, AIMS, and CDIIT total scores (all P<0.0001) and mean body weight (P=0.027) increased from baseline to 5 years. Putaminal 18F-DOPA PET uptake increased over time (P=0.0134). All patients experienced ≥1 TEAE, none considered PTC-AADC related, and mostly mild/moderate. Eight patients experienced 9 possibly/probably treatment-related dyskinesia episodes, generally in the first few months and resolving within 4 months. Seven patients experienced ≥1 serious AE, none PTC-AADC related. No deaths occurred during the study. No viral shedding was detected.
Conclusions:

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