Neuropediatrics 2019; 50(S 02): S1-S55
DOI: 10.1055/s-0039-1698240
Poster Presentations
Poster Area GNP Metabolic/Neurodegenerative Disorders
Georg Thieme Verlag KG Stuttgart · New York

AGIL-AADC Gene Therapy Results in Sustained Improvements in Motor and Developmental Milestones over 5 Years in Children with AADC Deficiency

Christian Werner
1   PTC Therapeutics Germany GmbH, Medical Affairs, Frankfurt, Germany
,
Yin-Hsiu Chien
2   National Taiwan University Hospital, Department of Medical Genetics and Pediatrics, Taipei, Taiwan
,
Ni-Chung Lee
2   National Taiwan University Hospital, Department of Medical Genetics and Pediatrics, Taipei, Taiwan
,
Sheng-Hong Tseng
2   National Taiwan University Hospital, Department of Medical Genetics and Pediatrics, Taipei, Taiwan
,
Chun-Hwei Tai
2   National Taiwan University Hospital, Department of Medical Genetics and Pediatrics, Taipei, Taiwan
,
Wuh-Liang Hwu
2   National Taiwan University Hospital, Department of Medical Genetics and Pediatrics, Taipei, Taiwan
,
Anne Marie Conway
3   PTC Therapeutics, Inc., Department of Biologics, South Plainfield, NJ, United States
,
Mark Pykett
4   PTC Therapeutics, Inc., Medical Affairs, South Plainfield, NJ, United States
› Author Affiliations
Further Information

Publication History

Publication Date:
11 September 2019 (online)

 
 

    Objective: To evaluate clinical outcomes through 5 years in children with aromatic L-amino acid decarboxylase (AADC) deficiency treated with AGIL-AADC, a recombinant adeno-associated virus vector containing the human cDNA encoding the AADC enzyme.

    Background: AADC deficiency is a rare genetic disorder of neurotransmitter synthesis. In this update, we present 2-year posttreatment data with AGIL-AADC in 18 patients, and 5-year posttreatment data for 8 patients.

    Design/Methods: In 2 single-arm, open-label clinical studies, children with AADC deficiency received AGIL-AADC (total dose, 1.8x10(11) 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 Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) also assessed developmental milestones. De novo dopamine production was evaluated with 6-[18F]fluorodopa PET imaging. Adverse events (AEs) were recorded. Findings were compared with those from a natural history cohort of severe AADC patients (n = 82) using the Fisher exact test (α = 0.05).

    Results: 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.

    Conclusions: In children with AADC deficiency, AGIL-AADC gene therapy achieved clinically meaningful, sustained improvements in motor, cognitive, and language milestones for up to 5 years, with no new safety signals identified.


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    No conflict of interest has been declared by the author(s).