Dados do Trabalho

Título

REDUCTIONS IN OCULOGYRIC CRISIS DURATION AND FREQUENCY IN CHILDREN WITH AROMATIC L-AMINO ACID DECARBOXYLASE DEFICIENCY TREATED WITH ELADOCAGENE EXUPARVOVEC GENE THERAPY: RESULTS FROM 3 CLINICAL TRIALS

Introdução

Aromatic L-Amino Acid Decarboxylase (AADC) deficiency is a rare autosomal recessive disorder resulting in marked dopamine loss, impeding normal motor development. A common symptom of AADC deficiency is oculogyric crises (OGC), which is frequently linked to decreased dopamine levels and characteristic involuntary eye movement. OGCs can also be accompanied by limb stiffness, torso rigidity, and autonomic signs. Eladocagene exuparvovec, a recombinant adeno-associated virus vector containing the human cDNA encoding the AADC enzyme, was studied in 3 AADC clinical trials.

Objetivo

To evaluate the duration (h/wk) and frequency (episodes/wk) of OGC episodes at baseline and 3 to 12 months in children with AADC deficiency after treated with Eladocagene exuparvovec.

Métodos

Eladocagene exuparvovec was administered as a bilateral infusion in the putamen of 28 children with AADC deficiency in 3 clinical trials (AADC-CU/1601 [8 patients, completed], AADC-010 [10 patients, ongoing], and AADC-011 [10 patients to date; ongoing]). Patients received a total of 1.8 × 1011 vg (n=21) or 2.4 × 1011 vg (n=7; AADC-011)]. Duration (h/wk) and frequency (episodes/wk) of OGC episodes were calculated at baseline and 3 to 12 months after gene therapy.

Resultados

Burden of OGC episodes decreased steadily following treatment with eladocagene exuparvovec. At baseline, mean duration of OGC episodes was 12.58 h/wk (n=22). OGC was reduced from baseline by a mean of 2.08 h/wk at 3 months (n=20), 2.24 h/wk at 6 months (n=12), 3.2h/wk at 9 months (n=12), and 3.64 h/wk at 12 months (n=8). At baseline, mean frequency of OGC was 2.63 episodes/wk (n=22). By month 3, the mean frequency decreased to 1.93 episodes/wk (n=20), by month 6, it was 1.9 episodes/wk (n=12) and remained at ~2 episodes/wk from months 9 to 12.

Conclusões

These results indicate a pattern of steady and sustained decrease over time in OGC episodes after PTC-AADC gene therapy. Reduced OGC has the potential to improve quality of life for patients with AADC deficiency and their caregivers by decreasing clinical burden.

Palavras Chave

AADC Deficiency. Neurotransmitter Disorder. Oculogyric Crisis. Gene Therapy.

Referências (se houver)

Fonte de Fomento (se houver)

Declaração de conflito de interesses de TODOS os autores

Paul Wuh-Liang Hwu has received research grants and honorarium from PTC Therapeutics, GTC, Inc. Antonia Wang and Traci Schilling are employees of PTC Therapeutics, Inc., South Plainfield, NJ. Luciana Giugliani and Pedro Pachelli are employees of PTC Farmacêutica do Brasil LTDA. Yin-Hsiu Chien, Ni-Chung Lee, Sheng-Hong Tseng, and Chun-Hwei Tai have nothing to disclose.

Área

Neurogenética