AADC deficiency: occurring in humans, modeled in rodents.
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.
Department of Pediatrics and Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: hwuwlntu@ntu.edu.tw.
Wuh-Liang
WL
Hwu
Ni-Chung
NC
Lee
Yin-Hsiu
YH
Chien
Shin-ichi
S
Muramatsu
Hiroshi
H
Ichinose
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000172:deficiency*; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006801:Humans; D051379:Mice
D001142:Aromatic-L-Amino-Acid Decarboxylases
Adeno-associated virus (AAV); Aromatic l-amino acid decarboxylase (AADC); Dopamine; Gene therapy; Mouse model; Neurotransmitter