Gene therapy for aromatic L-amino acid decarboxylase deficiency
Journal
Science Translational Medicine
Journal Volume
4
Journal Issue
134
Pages
134ra61
Date Issued
2012
Author(s)
Muramatsu S.-I.
KAI-YUAN TZEN
Snyder R.O.
Byrne B.J.
Abstract
Aromatic L-amino acid decarboxylase (AADC) is required for the synthesis of the neurotransmitters dopamine and serotonin. Children with defects in the AADC gene show compromised development, particularly in motor function. Drug therapy has only marginal effects on some of the symptoms and does not change early childhood mortality. Here, we performed adeno-associated viral vector-mediated gene transfer of the human AADC gene bilaterally into the putamen of four patients 4 to 6 years of age. All of the patients showed improvements in motor performance: One patient was able to stand 16 months after gene transfer, and the other three patients achieved supported sitting 6 to 15 months after gene transfer. Choreic dyskinesia was observed in all patients, but this resolved after several months. Positron emission tomography revealed increased uptake by the putamen of 6-[18F]fluorodopa, a tracer for AADC. Cerebrospinal fluid analysis showed increased dopamine and serotonin levels after gene transfer. Thus, gene therapy targeting primary AADC deficiency is well tolerated and leads to improved motor function.
SDGs
Other Subjects
6 fluorodopa f 18; aromatic levo amino acid decarboxylase; parvovirus vector; AADC gene; adolescent; apnea; aromatic levo amino acid decarboxylase deficiency; article; brain function; brain region; cerebrospinal fluid analysis; child; child development; clinical article; clinical evaluation; cognition; cyanosis; drug efficacy; enzyme deficiency; female; gene; gene mutation; gene therapy; human; male; motor performance; orofacial dyskinesia; positron emission tomography; priority journal; putamen; school child; treatment response; viral gene delivery system; Amino Acid Metabolism, Inborn Errors; Antibodies; Aromatic-L-Amino-Acid Decarboxylases; Child; Child, Preschool; Demography; Dependovirus; Dihydroxyphenylalanine; Female; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Male; Motor Activity; Neurotransmitter Agents; Positron-Emission Tomography; Taiwan
Type
journal article