Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism.

Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. Research Abstract Details 

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Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. Abstract Text:

Marina E Emborg,Maren Carbon,James E Holden,Matthew J During,Yilong Ma,Chengke Tang,Jeffrey Moirano,Helen Fitzsimons,Ben Z Roitberg,Eray Tuccar,Andrew Roberts,Michael G Kaplitt,David Eidelberg,

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 x 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.

Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. Publishing Authors By Initials

ME Emborg,M Carbon,JE Holden,MJ During,Y Ma,C Tang,J Moirano,H Fitzsimons,BZ Roitberg,E Tuccar,A Roberts,MG Kaplitt,D Eidelberg,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of cerebral blood flow and metabolism : of

VOLUME: 27

Page Numbers: 501-9

Journal Abbreviation: J. Cereb. Blood Flow Metab.

ISSN: 0271-678X

DAY: 12

MONTH: 07

YEAR: 2006

Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8112566

Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: pathology

Chemical & Substance for Abstract: Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. Information

Substance Name: Glutamate Decarboxylase

Registry Number: EC 4.1.1.15

Grant and Affiliation Information for Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism.

AFFILIATION: Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R01 NS 40578

ACRONYM: NS

MEDLINETA: J Cereb Blood Flow Metab

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