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Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson’s disease
- Publication Year :
- 2017
- Publisher :
- American Society for Clinical Investigation, 2017.
-
Abstract
- BACKGROUND. We report the 12-month clinical and imaging data on the effects of bilateral delivery of the glutamic acid decarboxylase gene into the subthalamic nuclei (STN) of advanced Parkinson's disease (PD) patients. METHODS. 45 PD patients were enrolled in a 6-month double-blind randomized trial of bilateral AAV2-GAD delivery into the STN compared with sham surgery and were followed for 12 months in open-label fashion. Subjects were assessed with clinical outcome measures and 18F-fluorodeoxyglucose (FDG) PET imaging. RESULTS. Improvements under the blind in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in the AAV2-GAD group compared with the sham group continued at 12 months [time effect: F(4,138) = 11.55, P < 0.001; group effect: F(1,35) = 5.45, P < 0.03; repeated-measures ANOVA (RMANOVA)]. Daily duration of levodopa-induced dyskinesias significantly declined at 12 months in the AAV2-GAD group (P = 0.03; post-hoc Bonferroni test), while the sham group was unchanged. Analysis of all FDG PET images over 12 months revealed significant metabolic declines (P < 0.001; statistical parametric mapping RMANOVA) in the thalamus, striatum, and prefrontal, anterior cingulate, and orbitofrontal cortices in the AAV2-GAD group compared with the sham group. Across all time points, changes in regional metabolism differed for the two groups in all areas, with significant declines only in the AAV2-GAD group (P < 0.005; post-hoc Bonferroni tests). Furthermore, baseline metabolism in the prefrontal cortex (PFC) correlated with changes in motor UPDRS scores; the higher the baseline PFC metabolism, the better the clinical outcome. CONCLUSION. These findings show that clinical benefits after gene therapy with STN AAV2-GAD in PD patients persist at 12 months. TRIAL REGISTRATION. ClinicalTrials.gov NCT00643890. FUNDING. Neurologix Inc.
- Subjects :
- 0301 basic medicine
Adult
Male
medicine.medical_specialty
Parkinson's disease
Glutamate decarboxylase
Urology
Statistical parametric mapping
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
Double-Blind Method
law
Parvovirinae
Subthalamic Nucleus
Medicine
Humans
Prefrontal cortex
Aged
business.industry
Glutamate Decarboxylase
Sham surgery
Gene Transfer Techniques
Parkinson Disease
General Medicine
Genetic Therapy
Dependovirus
Middle Aged
medicine.disease
United States
nervous system diseases
Clinical trial
030104 developmental biology
Treatment Outcome
Positron-Emission Tomography
Female
Analysis of variance
Clinical Medicine
business
030217 neurology & neurosurgery
Follow-Up Studies
Subjects
Details
- Language :
- English
- ISSN :
- 00643890
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....572a23197004ab897af1d757a33c9826