ICNC Abstracts, ICNC 2018

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Gene therapy improves global development in AADC deficiency
Takanori Yamagata, Karin Kojima, Akihiko Miyauchi, Takeshi Nakajima, Naoyuki Taga, Sachie Nakamura, Mitsuhiro Kato, Hitoshi Osaka, Shin-ichi Muramatsu

Last modified: 2018-09-09


Patients with aromatic l-amino acid decarboxylase (AADC) exhibit oculogyric crises, dystonia, impaired voluntary movements and intellectual disability from deficiency of catecholamines and serotonin. We performed gene therapy for seven patients with AADC deficiency and their phenotypes improved.

Patients and Methods: Six severe patients (4-19 year-old) who were bedridden with no voluntary movements nor speech, and one moderate patient (5-year-old) who could walk with support and speak several words were treated. They received 2 × 1011 vector genomes of adeno-associated virus (AAV) vector harboring AADC gene via bilateral intraputaminal infusions.

Results: By two years after gene therapy, motor function was improved and dystonia disappeared in all patients. Three severe patients walked with a walker, and the moderate patient could run and ride a bicycle. The moderate patient became able to converse. No adverse event was observed except for transient chorea. Positron emission tomography with 6-[18F]fluoro-l-m-tyrosine, a tracer of AADC, showed persistent AADC expression after gene therapy.

Discussion: Since the putamen is the main output structure of the motor network in the basal ganglia, improved motor performance and amelioration of dystonia can be expected. Further, cognitive and speech functions remarkably improved in the moderate patient. The effects may depend on the patient age at treatment and genetic severity. Gene therapy using AAV was shown to be safe and effective. There are many candidate diseases that gene therapy is expected to be effective in child neurological diseases. We are developing gene therapy for several diseases including GLUT1 deficiency syndrome.


gene therapy; L-amino acid decarboxylase (AADC) deficiency; aden-associated virus vector

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