Dataset Information

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.

SUBMITTER: Francois-Heude MC

PROVIDER: S-EPMC10187009 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

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

François-Heude Marie-Céline MC Poulen Gaetan G Flamand Roze Emmanuel E Nguyen Morel Marie-Ange MA Gras Domitille D Roch-Toreilles Isabelle I Quintard Adeline A Baroux Gaelle G Meyer Pierre P Coubes Philippe P Milesi Christophe C Cambonie Gilles G Baleine Julien J Sola Chrystelle C Delye Bénédicte B Dimopoulou Evgenia E Sanchez Stéphanie S Gasnier Mathieu M Touati Souad S Zamora Alberto A Pontal Daniel D Leboucq Nicolas N Kouyoumdjian Virginie V Lebasnier Adrien A Sanquer Sylvia S Mariano-Goulart Denis D Roujeau Thomas T Roubertie Agathe A

Movement disorders clinical practice 20230224 5

<h4>Background</h4>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).<h4>Objective</h4>We describe the clinical, biological, and imaging evolution of two AADCD patients ages >10 years after GD.<h4>Methods</h4>Eladocagene exuparvovec, a recombinant adeno-associat ...[more]

PMID: 37205256

Similar Datasets

Project description:In patients with aromatic l-amino acid decarboxylase (AADC) deficiency, a decrease in catecholamines and serotonin levels in the brain leads to developmental delay and movement disorders. The beneficial effects of gene therapy in patients from 1 to 8 years of age with homogeneous severity of disease have been reported from Taiwan. We conducted an open-label phase 1/2 study of population including adolescent patients with different degrees of severity. Six patients were enrolled: four males (ages 4, 10, 15 and 19 years) and one female (age 12 years) with a severe phenotype who were not capable of voluntary movement or speech, and one female (age 5 years) with a moderate phenotype who could walk with support. The patients received a total of 2 × 1011 vector genomes of adeno-associated virus vector harbouring DDC via bilateral intraputaminal infusions. At up to 2 years after gene therapy, the motor function was remarkably improved in all patients. Three patients with the severe phenotype were able to stand with support, and one patient could walk with a walker, while the patient with the moderate phenotype could run and ride a bicycle. This moderate-phenotype patient also showed improvement in her mental function, being able to converse fluently and perform simple arithmetic. Dystonia disappeared and oculogyric crisis was markedly decreased in all patients. The patients exhibited transient choreic dyskinesia for a couple of months, but no adverse events caused by vector were observed. PET with 6-[18F]fluoro-l-m-tyrosine, a specific tracer for AADC, showed a persistently increased uptake in the broad areas of the putamen. In our study, older patients (>8 years of age) also showed improvement, although treatment was more effective in younger patients. The genetic background of our patients was heterogeneous, and some patients suspected of having remnant enzyme activity showed better improvement than the Taiwanese patients. In addition to the alleviation of motor symptoms, the cognitive and verbal functions were improved in a patient with the moderate phenotype. The restoration of dopamine synthesis in the putamen via gene transfer provides transformative medical benefit across all patient ages, genotypes, and disease severities included in this study, with the most pronounced improvements noted in moderate patients.10.1093/brain/awy331_video1awy331media15991361892001.

Dataset Information

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

Background

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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