Dados do Trabalho
ELADOCAGENE EXUPARVOVEC GENE THERAPY IMPROVES MOTOR DEVELOPMENT IN PATIENTS WITH AROMATIC L-AMINO ACID DECARBOXYLASE DEFICIENCY
Aromatic L-amino acid decarboxylase (AADC) deficiency is caused by mutations in the DDC gene reducing AADC enzyme activity causing motor and neurodevelopmental impairments.
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.
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.
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)
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National Taiwan University Hospital - - Taiwan, PTC Farmacêutica do Brasil LTDA - São Paulo - Brasil, PTC Therapeutics Inc - - Estados Unidos
PAUL WUH-LIANG HWU, YIN-HSIU CHIEN, NI-CHUNG LEE, PANAYIOTA TRIFILLIS , PEDRO EUGENIO PACHELLI, LUCIANA GIUGLIANI, ANDRESSA FEDERHEN, CHUN-HWEI TAI