Publication Type Academic Article
Authors Feigin A, Kaplitt M, Tang C, Lin T, Mattis P, Dhawan V, During M, Eidelberg D
Journal Proc Natl Acad Sci U S A
Volume 104
Issue 49
Pagination 19559-64
Date Published 11/27/2007
ISSN 1091-6490
Keywords Brain, Genetic Therapy, Glutamate Decarboxylase, Parkinson Disease
Abstract Parkinson's disease (PD) is characterized by elevated expression of an abnormal metabolic brain network that is reduced by clinically effective treatment. We used fluorodeoxyglucose (FDG) positron emission tomography (PET) to determine the basis for motor improvement in 12 PD patients receiving unilateral subthalamic nucleus (STN) infusion of an adenoassociated virus vector expressing glutamic acid decarboxylase (AAV-GAD). After gene therapy, we observed significant reductions in thalamic metabolism on the operated side as well as concurrent metabolic increases in ipsilateral motor and premotor cortical regions. Abnormal elevations in the activity of metabolic networks associated with motor and cognitive functioning in PD patients were evident at baseline. The activity of the motor-related network declined after surgery and persisted at 1 year. These network changes correlated with improved clinical disability ratings. By contrast, the activity of the cognition-related network did not change after gene transfer. This suggests that modulation of abnormal network activity underlies the clinical outcome observed after unilateral STN AAV-GAD gene therapy. Network biomarkers may be used as physiological assays in early-phase trials of experimental therapies for PD and other neurodegenerative disease.
DOI 10.1073/pnas.0706006104
PubMed ID 18042721
PubMed Central ID PMC2148328
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