Gene Therapy for <scp>Amino Acid Decarboxylase</scp> Deficiency: Clinical and Imaging Outcomes in a French Cohort
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.
Authors
- Domitille Gras (ORCID: https://orcid.org/0000-0002-1843-7193)
- Emmanuel Flamand Roze (ORCID: https://orcid.org/0000-0001-9727-3459)
- Gaëtan Poulen (ORCID: https://orcid.org/0000-0001-5637-2004)
- Mohamed O E Babiker (ORCID: https://orcid.org/0000-0003-1277-6298)
- V. SZABO (ORCID: https://orcid.org/0000-0002-0079-7596)
- G Baroux
- Pierre Meyer (ORCID: https://orcid.org/0000-0001-5710-7376)
- Sylvia Sanquer (ORCID: https://orcid.org/0000-0002-0347-6501)
- Christophe Milési (ORCID: https://orcid.org/0000-0001-7714-5054)
- Adeline Quintard
- Chrystelle Sola (ORCID: https://orcid.org/0000-0002-8375-9121)
- Bénédicte Delye
- Mohammed Almuqbil (ORCID: https://orcid.org/0000-0002-6057-9603)
- Virginie Kouyoumdjian
- Souad Touati
- Julien Baleine (ORCID: https://orcid.org/0000-0001-6514-0571)
- Thomas Roujeau (ORCID: https://orcid.org/0000-0001-9569-7557)
- Philippe Coubes (ORCID: https://orcid.org/0000-0002-3152-3483)
- Clément Dunoyer
- Denis Mariano‐Goulart (ORCID: https://orcid.org/0000-0001-7044-2961)
- Jana Haberlová (ORCID: https://orcid.org/0000-0003-2734-9715)
- Eline Chauvet-Piat
- Bérénice Lecardonnel
- Nicolas Leboucq
- Stéphanie Sanchez
- Marie‐Céline François‐Heude
- Agathe Roubertie
- Marie‐Ange Nguyen Morel
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- King Saud bin Abdulaziz University for Health Sciences (SA)
- Université de Montpellier (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Al Jalila Foundation (AE)
- Agence France-Presse (FR)
- Sorbonne Université (FR)
- Hôpital Couple Enfant (FR)
- Centre Hospitalier Universitaire de Montpellier (FR)
- University Hospital in Motol (CZ)
- Institut des Sciences du Vivant Frédéric Joliot (FR)
- University Hospital of Geneva (CH)
- Hôpital Gui de Chauliac (FR)
- Pitié-Salpêtrière Hospital (FR)
- CEA Paris-Saclay (FR)
- Institut de Psychiatrie et Neurosciences de Paris (FR)
- Institute for Neurosciences of Montpellier (FR)
- Bicêtre Hospital (FR)
- Geneva College (US)
- Université Grenoble Alpes (FR)
Publication Details
- Journal
- Movement Disorders
- Published
- 2026-07-02
- DOI
- https://doi.org/10.1002/mds.70422
- Primary Topic
- Metabolism and Genetic Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00