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Gene therapy for aromatic L-amino acid decarboxylase deficiency

Wuh-Liang Hwu1, Shin-ichi Muramatsu, Sheng-Hong Tseng

  • 1Department of Pediatrics and Medical Genetics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 100, Taiwan. hwuwlntu@ntu.edu.tw

Science Translational Medicine
|May 18, 2012
PubMed

Insights

Gene therapy successfully restored motor function in children with Aromatic L-amino acid decarboxylase (AADC) deficiency. This treatment involved transferring the AADC gene, leading to improved neurotransmitter levels and developmental progress.

Area of Science:

  • Neurology
  • Genetics
  • Biochemistry

Background:

  • Aromatic L-amino acid decarboxylase (AADC) deficiency impairs dopamine and serotonin synthesis, causing severe motor development issues in children.
  • Current drug therapies offer limited benefits and do not impact mortality rates for AADC deficiency.

Purpose of the Study:

  • To evaluate the safety and efficacy of adeno-associated viral vector-mediated gene transfer of the human AADC gene in pediatric patients with AADC deficiency.

Main Methods:

  • Gene therapy was administered bilaterally into the putamen of four young patients (4-6 years old) using adeno-associated viral vectors carrying the AADC gene.
  • Motor function, choreic dyskinesia, AADC activity via 6-[(18)F]fluorodopa PET scans, and neurotransmitter levels in cerebrospinal fluid were assessed post-treatment.

Main Results:

  • All patients demonstrated significant improvements in motor function, including standing and supported sitting, within 6 to 16 months post-gene transfer.
  • Transient choreic dyskinesia was observed but resolved naturally. Increased 6-[(18)F]fluorodopa uptake in the putamen and elevated dopamine and serotonin levels confirmed successful gene transfer and enzyme activity.

Conclusions:

  • Gene therapy targeting primary AADC deficiency is a well-tolerated and effective treatment strategy.
  • This approach leads to substantial improvements in motor function for children affected by AADC deficiency, offering a promising therapeutic avenue.

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