两名芳香族L-氨基酸脱羧酶缺乏症患者的脑内注射基因传递
Intraputaminal Gene Delivery in Two Patients with Aromatic L-Amino Acid Decarboxylase Deficiency.
作者信息
François-Heude Marie-Céline, Poulen Gaetan, Flamand Roze Emmanuel, Nguyen Morel Marie-Ange, Gras Domitille, Roch-Toreilles Isabelle, Quintard Adeline, Baroux Gaelle, Meyer Pierre, Coubes Philippe, Milesi Christophe, Cambonie Gilles, Baleine Julien, Sola Chrystelle, Delye Bénédicte, Dimopoulou Evgenia, Sanchez Stéphanie, Gasnier Mathieu, Touati Souad, Zamora Alberto, Pontal Daniel, Leboucq Nicolas, Kouyoumdjian Virginie, Lebasnier Adrien, Sanquer Sylvia, Mariano-Goulart Denis, Roujeau Thomas, Roubertie Agathe
机构信息
CHU Montpellier, Département de Neuropédiatrie Univ Montpellier Montpellier France.
Département de Neurochirurgie CHU Montpellier Montpellier France.
出版信息
Mov Disord Clin Pract. 2023 Feb 24;10(5):811-818. doi: 10.1002/mdc3.13685. eCollection 2023 May.
BACKGROUND
Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, early-onset, dyskinetic encephalopathy mostly reflecting a defective synthesis of brain dopamine and serotonin. Intracerebral gene delivery (GD) provided a significant improvement among AADCD patients (mean age, ≤6 years).
OBJECTIVE
We describe the clinical, biological, and imaging evolution of two AADCD patients ages >10 years after GD.
METHODS
Eladocagene exuparvovec, a recombinant adeno-associated virus containing the human complimentary DNA encoding the AADC enzyme, was administered into bilateral putamen by stereotactic surgery.
RESULTS
Eighteen months after GD, patients showed improvement in motor, cognitive and behavioral function, and in quality of life. Cerebral l-6-[F] fluoro-3, 4-dihydroxyphenylalanine uptake was increased at 1 month, persisting at 1 year compared to baseline.
CONCLUSION
Two patients with a severe form of AADCD had an objective motor and non-motor benefit from eladocagene exuparvovec injection even when treated after the age of 10 years, as in the seminal study.
背景
芳香族L-氨基酸脱羧酶缺乏症（AADCD）是一种罕见的早发性运动障碍性脑病，主要反映脑内多巴胺和5-羟色胺合成缺陷。脑内基因递送（GD）在AADCD患者（平均年龄≤6岁）中带来了显著改善。
目的
我们描述了两名年龄大于10岁的AADCD患者在基因递送后的临床、生物学和影像学演变情况。
方法
通过立体定向手术将eladocagene exuparvovec（一种含有编码AADC酶的人类互补DNA的重组腺相关病毒）注入双侧壳核。
结果
基因递送18个月后，患者的运动、认知和行为功能以及生活质量均有改善。与基线相比，脑内L-6-[F]氟-3,4-二羟基苯丙氨酸摄取在1个月时增加，并持续至1年。
结论
两名严重形式的AADCD患者即使在10岁以后接受治疗，也从eladocagene exuparvovec注射中获得了客观的运动和非运动益处，与开创性研究中的情况相同。
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