Intraputaminal Gene Delivery in Two Patients with Aromatic L‐Amino Acid Decarboxylase Deficiency
Marie‐Céline François‐Heude, Gaëtan Poulen, Emmanuel Flamand Roze, Marie‐Ange Nguyen Morel, Domitille Gras, Isabelle Roch‐Toreilles, Adeline Quintard, G Baroux, Pierre Meyer, Philippe Coubes, Christophe Milési, Gilles Cambonie, Julien Baleine, Chrystelle Sola, Bénédicte Delye, Evgenia Dimopoulou, Stephanie Eugenia Ordonez Sanchez, Mathieu Gasnier, Souad Touati, Alberto Zamora, Daniel Pontal, Nicolas Leboucq, Virginie Kouyoumdjian, Adrien Lebasnier, Sylvia Sanquer, Denis Mariano‐Goulart, Thomas Roujeau, Agathe Roubertie
Abstract
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‐[ 18 F] 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.