title: 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.affiliation: Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mittermeyer
authors.forename: Chadwick W
authors.initials: CW
authors.lastname: Christine
authors.forename: Kathryn H
authors.initials: KH
authors.lastname: Rosenbluth
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Baker
authors.forename: Philip
authors.initials: P
authors.lastname: Starr
authors.forename: Paul
authors.initials: P
authors.lastname: Larson
authors.forename: Paul L
authors.initials: PL
authors.lastname: Kaplan
authors.forename: John
authors.initials: J
authors.lastname: Forsayeth
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Aminoff
authors.forename: Krystof S
authors.initials: KS
authors.lastname: Bankiewicz
mesh_terms: D000368:Aged; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D000229:Dependovirus / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy*; D049268:Positron-Emission Tomography
chemical_list: D001142:Aromatic-L-Amino-Acid Decarboxylases