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

Abstract

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.

• Authors: Gabriele Mittermeyer, Chadwick W Christine, Kathryn H Rosenbluth, Suzanne L Baker, Philip Starr, Paul Larson, Paul L Kaplan, John Forsayeth, Michael J Aminoff, Krystof S Bankiewicz
• Journal: Human gene therapy (Hum Gene Ther) Vol. 23 Issue 4 Pg. 377-81 (Apr 2012) ISSN: 1557-7422 [Electronic] United States
• PMID: 22424171 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aromatic-L-Amino-Acid Decarboxylases

Topics

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