Clinical improvements in the first year following eladocagene exuparvovec gene therapy in patients with aromatic L-amino acid decarboxylase deficiency

Objectives: The purpose of this post hoc analysis was to evaluate clinical outcomes in patients with the rare genetic disorder aromatic L-amino acid decarboxylase (AADC) deficiency during the first year after eladocagene exuparvovec gene therapy administration.

Methods: Eladocagene exuparvovec was administered bilaterally into the putamen of 28 patients with AADC deficiency in 3 open-label clinical trials. Patients received 1.8 × 10^11 vg (n=21) or 2.4 × 10^11 vg (n=7). Gross motor milestone development was evaluated using the Peabody Developmental Motor Scale–Second Edition. Physical and neurological exam data were used to evaluate swallowing function, body weight, autonomic symptoms, movement disorder symptoms, and rate of respiratory infections at baseline and ≤12-month follow-up.

Results: At baseline, 21% (6/28) of patients achieved partial head control. Within 12 months, 89% (25/28) achieved partial or full head control, 43% (12/28) could sit assisted or unassisted, and 4% (1/28) were able to stand with support. Among patients with available feeding data, 80% (8/10) showed improvements in swallowing function. This improvement was mirrored by increases in body weight and reduced rates of respiratory infection. The proportion of patients experiencing symptoms related to autonomic dysfunction and movement disorders also decreased from baseline to 12 months.

Conclusions: In this post hoc analysis of the ≤12 months following eladocagene exuparvovec delivery, patients demonstrated improvements in various symptoms of AADC deficiency. Specifically, swallowing function, body weight, rate of respiratory infection, autonomic dysfunction, and movement disorder–related symptoms improved. Patients also attained critical gross motor milestones that were not present at baseline.
Keywords: Rare Diseases, Genetics, Gene Therapy, Movement Disorders