Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency

Mol Ther. 2022 Feb 2;30(2):509-518. doi: 10.1016/j.ymthe.2021.11.005. Epub 2021 Nov 8.


Aromatic L-amino acid decarboxylase deficiency results in decreased neurotransmitter levels and severe motor dysfunction. Twenty-six patients without head control received bilateral intraputaminal infusions of a recombinant adeno-associated virus type 2 vector containing the human aromatic L-amino acid decarboxylase gene (eladocagene exuparvovec) and have completed 1-year evaluations. Rapid improvements in motor and cognitive function occurred within 12 months after gene therapy and were sustained during follow-up for >5 years. An increase in dopamine production was demonstrated by positron emission tomography and neurotransmitter analysis. Patient symptoms (mood, sweating, temperature, and oculogyric crises), patient growth, and patient caretaker quality of life improved. Although improvements were observed in all treated participants, younger age was associated with greater improvement. There were no treatment-associated brain injuries, and most adverse events were related to underlying disease. Post-surgery complications such as cerebrospinal fluid leakage were managed with standard of care. Most patients experienced mild to moderate dyskinesia that resolved in a few months. These observations suggest that eladocagene exuparvovec treatment for aromatic L-amino acid decarboxylase deficiency provides durable and meaningful benefits with a favorable safety profile.

Trial registration: ClinicalTrials.gov NCT01395641 NCT02926066.

Keywords: adeno-associated virus; aromatic L-amino acid decarboxylase deficiency; eladocagene exuparvovec; gene therapy; putamen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Metabolism, Inborn Errors* / diagnosis
  • Amino Acid Metabolism, Inborn Errors* / genetics
  • Amino Acid Metabolism, Inborn Errors* / therapy
  • Aromatic-L-Amino-Acid Decarboxylases / cerebrospinal fluid
  • Aromatic-L-Amino-Acid Decarboxylases / deficiency
  • Aromatic-L-Amino-Acid Decarboxylases / genetics
  • Dopamine
  • Genetic Therapy / adverse effects
  • Humans
  • Quality of Life*


  • Aromatic-L-Amino-Acid Decarboxylases
  • Dopamine

Supplementary concepts

  • Aromatic amino acid decarboxylase deficiency

Associated data

  • ClinicalTrials.gov/NCT01395641
  • ClinicalTrials.gov/NCT02926066