AADC deficiency. Occurring in humans, modeled in rodents.
Journal
Advances in Pharmacology
Journal Volume
68
Pages
273-284
Date Issued
2013
Author(s)
Abstract
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. ? 2013 Elsevier Inc.
SDGs
Other Subjects
3,4 dihydroxyphenylacetic acid; 5 hydroxyindoleacetic acid; amine oxidase (flavin containing); aromatic levo amino acid decarboxylase; DOPA; dopamine; homodimer; homovanillic acid; neurotransmitter; parvovirus vector; pyridoxal 5 phosphate; serotonin; anxiety; article; autonomic dysfunction; disease model; enzyme deficiency; experimental mouse; gene therapy; gene transfer; human; infancy; motor development; nonhuman; priority journal; survival rate; weight gain; Adeno-associated virus (AAV); Aromatic l-amino acid decarboxylase (AADC); Dopamine; Gene therapy; Mouse model; Neurotransmitter; Animals; Aromatic-L-Amino-Acid Decarboxylases; Dependovirus; Disease Models, Animal; Genetic Therapy; Humans; Mice
Publisher
Academic Press Inc.
Type
book part