Long-term follow-up of a randomized AAV2- gene therapy trial for Parkinson's disease.

TitleLong-term follow-up of a randomized AAV2- gene therapy trial for Parkinson's disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsNiethammer M, Tang CC, LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Sarkar A, Siddiqui MS, Tatter SB, Schwalb JM, Poston KL, Henderson JM, Kurlan RM, Richard IH, Sapan CV, Eidelberg D, During MJ, Kaplitt MG, Feigin A
JournalJCI Insight
Date Published2017 04 06
KeywordsAdult, Aged, Double-Blind Method, Female, Follow-Up Studies, Gene Transfer Techniques, Genetic Therapy, Glutamate Decarboxylase, Humans, Male, Middle Aged, Parkinson Disease, Parvovirinae, Positron-Emission Tomography, Subthalamic Nucleus, Treatment Outcome, United States

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. 45 PD patients were enrolled in a 6-month double-blind randomized trial of bilateral AAV2- 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 F-fluorodeoxyglucose (FDG) PET imaging. Improvements under the blind in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in the AAV2- group compared with the sham group continued at 12 months [time effect: (4,138) = 11.55, < 0.001; group effect: (1,35) = 5.45, < 0.03; repeated-measures ANOVA (RMANOVA)]. Daily duration of levodopa-induced dyskinesias significantly declined at 12 months in the AAV2- group ( = 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 ( < 0.001; statistical parametric mapping RMANOVA) in the thalamus, striatum, and prefrontal, anterior cingulate, and orbitofrontal cortices in the AAV2- 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- group ( < 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. These findings show that clinical benefits after gene therapy with STN AAV2- in PD patients persist at 12 months. ClinicalTrials.gov NCT00643890. Neurologix Inc.

Alternate JournalJCI Insight
PubMed ID28405611
PubMed Central IDPMC5374069