Long-Term Evaluation of a Phase 1 Study of AADC Gene Therapy for Parkinson's Disease
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- 1 April 2012
- journal article
- research article
- Published by Mary Ann Liebert Inc in Human Gene Therapy
- Vol. 23 (4), 377-381
- https://doi.org/10.1089/hum.2011.220
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 [18F]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. Mittermeyer and colleagues report results from a phase 1 study of AAV2-hAADC (human aromatic l-amino acid decarboxylase) gene therapy for the treatment of Parkinson's disease. The study shows that AAV2-hAADC treatment was safe and that AADC gene expression was maintained at least 4 years after administration of therapy. Positron emission tomography analysis showed that a similar number of neurons continued expressing the transgene throughout the study.Keywords
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