Dados do Trabalho

Título

SAFETY AND IMPROVED EFFICACY OUTCOMES IN CHILDREN WITH AADC DEFICIENCY TREATED WITH AGIL-AADC GENE THERAPY: RESULTS FROM THREE CLINICAL TRIALS

Introdução

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disorder of neurotransmitters dopamine and serotonin synthesis, is characterized by motor developmental deficits and clinical features associated with the autonomic nervous system, including dyskinesia, oculogyric crisis, and feeding/swallowing problems.

Objetivo

To evaluate clinical outcomes in children with AADC deficiency treated with AGIL-AADC, a recombinant adeno-associated virus vector containing the human cDNA encoding the AADC enzyme.

Métodos

In 3 open-label clinical studies, children with AADC deficiency who had no full head control and no ability to sit, stand, or walk received AGIL-AADC as bilateral, intraputaminal, stereotactic infusions during a single operative session (total dose, 1.8x1011 vg). Body weight, oculogyric crisis episodes, and adverse events (AEs) were recorded.

Resultados

In the 3 studies, patients aged 21 months to 8.5 years (N=26) received AGIL-AADC, constituting the safety population. In the intent-to-treat population (N=21), mean body weight at baseline was 12.0 kg (median 10.5 kg) and increased to 15.2 kg (median 13.2 kg) at 12 months posttreatment. Frequency of oculogyric crises was improved at 12 months posttreatment. Dyskinesia was recorded as an AE in 23 patients in the safety population; most events were mild or moderate, occurred within 3 months after AGIL-AADC treatment, and resolved in all patients by 10 months.

Conclusões

In children with AADC deficiency who received AGIL-AADC gene therapy, body weight increased and oculogyric crises and dyskinesia improved, suggesting that gene therapy achieved clinically meaningful with a good safety profile.

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

Área

Neurogenética