Gene Therapy for Aromatic L-Amino Acid Decarboxylase Deficiency
Resource
Sci. Transl. Med., 4(134)
Journal
Neurosurgery
Pages
N10-N12
Date Issued
2012
Date
2012
Author(s)
Hwu, Wuh-Liang
Muramatsu, Shin-ichi
Tseng, Sheng-Hong
Tzen, Kai-Yuan
Lee, Ni-Chung
Chien, Yin-Hsiu
Snyder, Richard O.
Byrne, Barry J.
Tai, Chun-Hwei
Wu, Ruey-Meei
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-[F-18] 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.
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