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...

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Published in:Movement disorders clinical practice (Hoboken, N.J.) N.J.), 2023-05, Vol.10 (5), p.811-818
Main Authors: François‐Heude, Marie‐Céline, Poulen, Gaetan, Flamand Roze, Emmanuel, Nguyen Morel, Marie‐Ange, Gras, Domitille, Roch‐Toreilles, Isabelle, Quintard, Adeline, Baroux, Gaelle, Meyer, Pierre, Coubes, Philippe, Milesi, Christophe, Cambonie, Gilles, Baleine, Julien, Sola, Chrystelle, Delye, Bénédicte, Dimopoulou, Evgenia, Sanchez, Stéphanie, Gasnier, Mathieu, Touati, Souad, Zamora, Alberto, Pontal, Daniel, Leboucq, Nicolas, Kouyoumdjian, Virginie, Lebasnier, Adrien, Sanquer, Sylvia, Mariano‐Goulart, Denis, Roujeau, Thomas, Roubertie, Agathe
Format: Article
Language:English
Subjects:
AADC deficiency
Amino acids
Brief Report
Brief Reports
elodecagene exuparvovec
Gene therapy
Human health and pathology
Life Sciences
Movement disorders
Neurons and Cognition
oculogyric crisis
Surgery
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Summary: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.
ISSN:2330-1619
2330-1619
DOI:10.1002/mdc3.13685