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 DDC gene reducing AADC enzyme activity causing motor and neurodevelopmental impairments.

Objetivo

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

Método

Therapy was infused bilaterally in the putamina of 30 patients aged 18–102 months receiving 1.8 × 1011 vg (n=21) or 2.4 × 1011 vg (n=9) followed for up to 120 months assessed using PDMS-2 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 were measured every 3 months for 1 year following gene therapy, then every 6–12 months for ≤120 months. Data extracted on January 4, 2022.

Resultados e Conclusões

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 upstairs (3). These abilities were maintained for as long as 10 years.
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).

Declaração de conflito de interesses de TODOS os autores

PW-LH has received research grants from and served as an advisory board member and consulted for PTC Therapeutics Inc. Y-HC has served as an advisory board member for Amicus Therapeutics, Asklepios BioPharmaceutical, Biogen, Novartis, Sanofi and Takeda. She is or was a research investigator for Biogen and Sanofi, and is or was a consultant for Abeona Therapeutics, Biogen, Novartis and PTC Therapeutics Inc. She has also served as a speaker for Avexis, Biogen, BioMarin Pharmaceutical Inc., Novartis, Sanofi and Takeda. N-CL has consulted for PTC Therapeutics Inc. P-T is employee of PTC Therapeutics Inc. P-EP, L-G and A-F are employees of PTC Farmacêutica do Brasil LDTA. C-HT has nothing to disclose.

Fonte de Fomento (se houver)

The studies included in this presentation were funded in part by PTC Therapeutics Inc.

Referências (se houver)

Himmelreich N, et al. Mol Genet Metab 2019;127:12–22; Hwu WL et al. JIMD Rep 2018;40:1–6; Wassenberg T et al. Orphanet J Rare Dis 2017;12:12; Hwu WL et al. Sci Transl Med 2012;4:134ra61; Brun L et al. Neurology 2010;75:64–71; Hwu PWL et al. EMBO Mol Med 2021;13:e14712; Pearson TS et al. Nat Commun 2021;12:4251; PTC Therapeutics International Ltd. Summary of Product Characteritsics, Upstaza. European Medical Agency, 2022. Available from: https://www.ema.europa.eu/en/documents/product-information/upstaza-epar-product-information_en.pdf (Accessed August 31, 2022); Chien YH et al. Lancet Child Adolesc Health 2017;1:265–73; Tai CH et al. Mol Ther 2022;30:509–18; Folio MR, Fewell RR. Peabody Developmental Motor scales: Examiner's Manual. Pro-Ed 2000; Munetz MR, Benjamin S. Hosp Community Psychiatry 1988;39:1172–7.

Área

Neurogenética