Hwu Wuh-Liang, Lee Ni-Chung, Chien Yin-Hsiu, Muramatsu Shin-ichi, Ichinose Hiroshi
Department of Pediatrics and Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Adv Pharmacol. 2013;68:273-84. doi: 10.1016/B978-0-12-411512-5.00013-0.
Aromatic l-amino acid decarboxylase (AADC) is a homodimeric pyridoxal phosphate-dependent enzyme responsible for the syntheses of dopamine and serotonin. Defects in the AADC gene result in neurotransmitter deficiencies. Patients with AADC deficiency have severe motor and autonomic dysfunctions. A mouse model of AADC deficiency was recently established. These mice grow poorly and move awkwardly during infancy. They also show high anxiety when they grow up. Because drug therapy provides little or no benefit for many patients with AADC deficiency, a gene therapy has been attempted. The gene therapy employed an adeno-associated virus viral vector that can express the human AADC protein. The vector was injected to the brain of several children with AADC deficiency. The therapy was well tolerated, and all treated patients showed improvement. In the future, the mouse model will also help the development of treatments for AADC deficiency.
芳香族L-氨基酸脱羧酶（AADC）是一种同二聚体的磷酸吡哆醛依赖性酶，负责多巴胺和5-羟色胺的合成。AADC基因缺陷会导致神经递质缺乏。AADC缺乏症患者有严重的运动和自主神经功能障碍。最近建立了AADC缺乏症的小鼠模型。这些小鼠在婴儿期生长不良且行动笨拙。它们长大后还表现出高度焦虑。由于药物治疗对许多AADC缺乏症患者几乎没有益处，因此尝试了基因治疗。该基因治疗采用了一种能表达人AADC蛋白的腺相关病毒载体。将该载体注射到几名AADC缺乏症儿童的大脑中。该治疗耐受性良好，所有接受治疗的患者都有改善。未来，该小鼠模型也将有助于开发AADC缺乏症的治疗方法。
