Reductions in oculogyric crisis duration and frequency in children with aromatic L-amino acid decarboxylase deficiency treated with eladocagene exuparvovec: results from 3 clinical trials

Objectives: Aromatic L-Amino Acid Decarboxylase (AADC) deficiency is a rare autosomal recessive disorder resulting in marked dopamine loss, impeding normal motor development. Oculogyric crises (OGC) are involuntary eye movements characteristic of AADC deficiency, which are linked to decreased dopamine levels. OGCs can be accompanied by limb stiffness, torso rigidity, and autonomic signs. Eladocagene exuparvovec, a recombinant adeno-associated viral vector containing the human cDNA encoding the AADC enzyme, was studied in 3 AADC clinical trials.

Methods: Eladocagene exuparvovec was administered as a bilateral infusion in the putamen of 28 children with AADC deficiency in 3 trials (AADC-CU/1601 [8 patients, completed], AADC-010 [10 patients, completed], and AADC-011 [10 patients to date; ongoing]). Patients received a total of 1.8 × 10^11 vg (n=21) or 2.4 × 10^11 vg (n=7; AADC-011)]. Duration (h/wk) and frequency (episodes/wk) of OGC episodes were calculated at baseline and 3 to 12 months after treatment.

Results:. At baseline, mean duration of OGC episodes was 12.58 h/wk (n=22). OGC was reduced from baseline by a mean of 2.08 h/wk at 3 months (n=20), 2.24 h/wk at 6 months (n=12), 3.2h/wk at 9 months (n=12), and 3.64 h/wk at 12 months (n=8). At baseline, mean frequency of OGC was 2.63 episodes/wk (n=22). By month 3, the mean frequency decreased to 1.93 episodes/wk (n=20), by month 6, it was 1.9 episodes/wk (n=12), and remained at ~2 episodes/wk from months 9 to 12.

Conclusions: These results indicate a pattern of steady and sustained decrease over time in OGC episodes after PTC-AADC gene therapy.
Keywords: Rare Diseases, AADC Deficiency, Gene Therapy, Movement Disorders