Gene Therapy for
Amino Acid Decarboxylase
Deficiency: Clinical and Imaging Outcomes in a French Cohort
Clément Dunoyer, Gaëtan Poulen, Marie‐Céline François‐Heude, Eline Chauvet‐Piat, Bérénice Lecardonnel, Emmanuel Roze, Marie‐Ange Nguyen Morel, Domitille Gras, Adeline Quintard, Gaelle Baroux, Pierre Meyer, Philippe Coubes, Christophe Milesi, Julien Baleine, Chrystelle Sola, Vivien Szabo, Bénédicte Delye, Jana Haberlova, Mohamed Osman Eltahir Babiker, Mohammed Al Muqbil, Stéphanie Sanchez, Souad Touati, Nicolas Leboucq, Virginie Kouyoumdjian, Sylvia Sanquer, Denis Mariano‐Goulart, Thomas Roujeau, Agathe Roubertie Abstract
Background
Intracerebral gene therapy is effective for amino acid decarboxylase (AADC) deficiency, but relationships between anatomical putaminal coverage, metabolic dynamics, and clinical recovery remain poorly understood.
Objectives
Assess safety, long‐term efficacy, and clinical–radiological correlations in a genetically diverse European cohort of AADC deficiency.
Methods
Six patients received bilateral intraputaminal rAAV2‐hAADC infusion. Motor (GMFM‐88), functional (CP‐CHILD, Vineland‐II), oculogyric crises (OGC), and dyskinesia outcomes were evaluated alongside magnetic resonance imaging (MRI) volumetric coverage and longitudinal 18F‐fluorodopa (18F‐DOPA) positron emission tomography (PET) parameters.
Results
All patients achieved genotype‐independent motor improvements and OGC reduction, with no serious adverse events. Clinical recovery did not correlate with the putaminal coverage volume, indicating a biological threshold effect. Transient dyskinesias coincided with an early 18F‐DOPA uptake peak (1–3 months post‐operative), followed by clinical resolution and sustained activity, reflecting homeostatic synaptic plasticity.
Conclusion
Eladocagene exuparvovec offers durable clinical benefits across diverse genotypes. Therapeutic efficacy and the subsequent neuroplasticity sequence seem to depend on reaching a critical threshold of dopamine production rather than on exhaustive anatomical coverage of the putamen. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.