Dados do Trabalho

Título

ELADOCAGENE EXUPARVOVEC GENE THERAPY IMPROVES MOTOR DEVELOPMENT IN PATIENTS WITH AROMATIC L-AMINO ACID DECARBOXYLASE DEFICIENCY

Introdução

Aromatic L-amino acid decarboxylase (AADC) deficiency is caused by mutations in the dopa decarboxylase gene leading to reduced AADC enzyme activity; it is characterized by motor impairments and inability to attain developmental milestones.

Objetivo

To evaluate clinical outcomes in children with AADC treated with Eladocagene exuparvovec, a recombinant adeno-associated viral vector serotype 2 carrying the coding sequence for human AADC enzyme.

Métodos

Eladocagene exuparvovec was infused bilaterally in the putamina of 30 children with AADC deficiency in 3 clinical trials (AADC-CU/1601 [n=8], AADC-010 [n=10], and AADC-011 [n=12] in patients aged 18–102 months. Data were extracted on January 4, 2022. Patients receiving a total of 1.8 × 1011 vg (n=21) or 2.4 × 1011 vg (n=9; AADC-011) were followed for up to 120 months and assessed for motor milestone attainment using the Peabody Developmental Motor Scale, 2nd edition (PDMS-2). Specific motor skill items of the PDMS-2 were used to assess key motor milestones including head control (partial or full), sitting (supported or independently), standing (with/away from support; up from cross-legged position), and walking (with/without assistance; 10 feet; taped line) Motor milestones and development were measured every 3 months for 1 year following gene therapy, then every 6–12 months for ≤120 months.

Resultados

At baseline, no patients had mastered head control or more advanced milestones. At year 1 of follow-up, patients were gaining the following skills (n): partial head control (26); full head control (15), sitting unassisted (7), supported standing (2). Progression of development was noted at years 5 and 10. By year 5 of follow-up, more advanced milestones were achieved (n): full head control (24), sitting unassisted (21) assisted walking (5), walking 10 feet (3), or walking up stairs (3). These abilities were maintained for as long as 10 years.

Conclusões

The data indicate that eladocagene exuparvovec can provide a durable, positive impact on motor development in patients with AADC deficiency.

Palavras chave

Rare Diseases, Genetics, Movement Disorders (including Cerebral Palsy)

Referências (se houver)

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Fonte de Fomento (se houver)

Declaração de conflito de interesses de TODOS os autores

Paul Wuh-Liang Hwu participated as an advisory board member, received consulting fees, and was a speaker for PTCTherapeutics, BioMarin, and Sanofi; was a grant recipient for PTC Therapeutics and BioMarin; and was research investigator for PTC Therapeutics.
Agathe Roubertie has received consulting fees from PTC Therapeutics and GW Pharmaceuticals.
Antonia Wang, Alexis Russell, Andressa Federhen, and Pedro Eugenio Pachelli are employees and stock owner for PTC Farmacêutica do Brasil LTDA.
Yin-Hsiu Chien, Ni-Chung Lee, and Chun-Hwei Tai have nothing to disclose.

Área

Neurogenética