Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease.

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