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

Abstract

Background: Aromatic 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).

Objective: We describe the clinical, biological, and imaging evolution of two AADCD patients ages >10 years after GD.

Methods: Eladocagene exuparvovec, a recombinant adeno-associated virus containing the human complimentary DNA encoding the AADC enzyme, was administered into bilateral putamen by stereotactic surgery.

Results: Eighteen 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.

Conclusion: Two 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.

Keywords: AADC deficiency; elodecagene exuparvovec; gene therapy; oculogyric crisis.

FIG. 1

¹⁸F‐DOPA PET and MRI images at baseline, 1 month, and 1 year after gene delivery. The color palette was centered on the maximum signal observed in the cortical gray matter, to allow visual comparison between time points and patients. ¹⁸F‐DOPA PET scan visualizes the capacity of the neurons of the putamen to durably take up ¹⁸F‐DOPA, which implies an efficient decarboxylation of this amino acid. Increased fixation is observed 1 month and 1 year after gene delivery. ¹⁸F‐DOPA, l‐6‐[¹⁸F] fluoro‐3, 4‐dihydroxyphenylalanine; PET, positron emission tomography; MRI, magnetic resonance imaging.