Intraputaminal Gene Delivery in Two Patients with Aromatic L‐Amino Acid Decarboxylase Deficiency

Abstract

ABSTRACTBackgroundAromatic l‐amino acid decarboxylase deficiency (AADCD) is a rare, early‐onset, dyskinetic encephalopathy mostly reflecting a defective synthesis of brain dopamine and serotonin. Intracerebral gene delivery (GD) provided a significant improvement among AADCD patients (mean age, ≤6 years).ObjectiveWe describe the clinical, biological, and imaging evolution of two AADCD patients ages >10 years after GD.MethodsEladocagene exuparvovec, a recombinant adeno‐associated virus containing the human complimentary DNA encoding the AADC enzyme, was administered into bilateral putamen by stereotactic surgery.ResultsEighteen months after GD, patients showed improvement in motor, cognitive and behavioral function, and in quality of life. Cerebral l‐6‐[18F] fluoro‐3, 4‐dihydroxyphenylalanine uptake was increased at 1 month, persisting at 1 year compared to baseline.ConclusionTwo patients with a severe form of AADCD had an objective motor and non‐motor benefit from eladocagene exuparvovec injection even when treated after the age of 10 years, as in the seminal study.