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Subthalamic GlutamicAcid DecarboxylaseGene Therapy: Changesin Motor Function andCortical Metabolism Marina E. EmborgMaren CarbonJames E. Holden2006 год

Subthalamic Glutamic Acid Decarboxylase Gene Therapy: Changes in Motor Function and Cortical Metabolism
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Аннотация: Parkinson's disease (PD) is associated with increased excitatory activity within the subthalamic nucleus (STN). We sought to inhibit STN output in hemiparkinsonian macaques by transfection with adeno-associated virus (AAV) containing the gene for glutamic acid decarboxylase (GAD). In total, 13 macaques were rendered hemiparkinsonian by right intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection. Seven animals were injected with AAV-GAD into the right STN, and six received an AAV gene for green fluorescent protein (GFP). Videotaped motor ratings were performed in a masked fashion on a weekly basis over a 55-week period. At 56 weeks, the animals were scanned with 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Histological examination was performed at the end of the study. No adverse events were observed after STN gene therapy. We found that the clinical rating scores for the two treatment groups had different patterns of change over time (group × time interaction, P<0.001). On FDG PET, the GAD animals exhibited an increase in glucose utilization in the right motor cortex relative to GFP controls ( P<0.001). Metabolism in this region correlated with clinical ratings at end point ( P<0.01). Histology confirmed GAD expression in treated animals. These findings suggest that STN AAV-GAD is well tolerated and potentially effective in a primate model of PD. The changes in motor cortical glucose utilization observed after gene therapy are consistent with the modulation of metabolic brain networks associated with this disorder.
Год издания: 2006
Авторы: Marina E. Emborg, Maren Carbon, James E. Holden, Matthew J. During, Yilong Ma, Chengke Tang, Jeffrey M. Moirano, Helen L. Fitzsimons, Ben Roitberg, Eray Tüccar, Andrew D. Roberts, Michael G. Kaplitt, David Eidelberg
Издательство: SAGE Publishing
Источник: Journal of Cerebral Blood Flow & Metabolism
Ключевые слова: Neurological disorders and treatments, Parkinson's Disease Mechanisms and Treatments, Genetic Neurodegenerative Diseases
Другие ссылки: Journal of Cerebral Blood Flow & Metabolism (HTML)
PubMed (HTML)