Objective:

Investigate the  efficacy and safety of eladocagene exuparvovec in patients with aromatic l-amino acid decarboxylase  deficiency (AADCd).

Background:

AADCd results from mutations in the dopa decarboxylase gene leading to reduced AADC enzyme activity; it is characterized by motor impairments and inability to attain developmental milestones. Eladocagene exuparvovec is a recombinant adeno-associated viral vector serotype 2 carrying the coding sequence for human AADC.

Design/Methods:

Eladocagene exuparvovec was infused bilaterally in the putamina of 30 children with AADC deficiency in 3 studies (AADC-CU/1601 [n=8], AADC-010 [n=10], and AADC-011 [n=12] in patients aged 18–102 months. Data were extracted on January 4, 2022. Patients  receiving a total of 1.8 × 10¹¹ vg (n=21) or 2.4 × 10¹¹ vg (n=9; AADC-011) were followed for up to 120 months and assessed for motor milestone attainment using the Peabody Developmental Motor Scale, 2nd edition (PDMS-2). Specific motor skill items of the PDMS-2 were used to assess  motor milestones including head control (partial or full), sitting (supported or independently), standing (with/away from support; up from cross-legged position), and walking (with/without assistance; 10 feet; taped line) Motor milestones and development were measured every 3 months for 1 year following gene therapy, then every 6–12 months for ≤120 months.

Results:

At baseline, no patients  mastered head control or more advanced milestones. At year 1 of follow-up, patients were gaining the following skills (n): partial head control (26); full head control (15), sitting unassisted (7), supported standing (2). Progression of development was noted at years 5 and 10. By year 5, more advanced milestones were achieved (n): full head control (24), sitting unassisted (21) assisted walking (5), walking 10 feet (3), or walking up stairs (3). These abilities were maintained for as long as 10 years

Conclusions: