Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson's disease

Hum Gene Ther. 2012 Apr;23(4):377-81. doi: 10.1089/hum.2011.220. Epub 2012 Apr 10.


We report the results of a long-term follow-up of subjects in a phase 1 study of AAV2-hAADC (adeno-associated virus type 2-human aromatic L-amino acid decarboxylase) gene therapy for the treatment of Parkinson's disease (PD). Ten patients with moderately advanced PD received bilateral putaminal infusions of either a low or a high dose of AAV2-hAADC vector. An annual positron emission tomography (PET) imaging with [(18)F]fluoro-L-m-tyrosine tracer was used for evaluation of AADC expression, and a standard clinical rating scale [Unified Parkinson's Disease Rating Scale (UPDRS)] was used to assess effect. Our previous analysis of the 6-month data suggested that this treatment was acutely safe and well tolerated. We found that the elevated PET signal observed in the first 12 months persisted over 4 years in both dose groups. A significantly increased PET value compared with the presurgery baseline was maintained over the 4-year monitoring period. The UPDRS in all patients off medication for 12 hr improved in the first 12 months, but displayed a slow deterioration in subsequent years. This analysis demonstrates that apparent efficacy continues through later years with an acceptable safety profile. These data indicate stable transgene expression over 4 years after vector delivery and continued safety, but emphasize the need for a controlled efficacy trial and the use of a higher vector dose.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aromatic-L-Amino-Acid Decarboxylases / genetics*
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism
  • Cohort Studies
  • Dependovirus / genetics*
  • Female
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / genetics*
  • Parkinson Disease / therapy*
  • Positron-Emission Tomography


  • Aromatic-L-Amino-Acid Decarboxylases