Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease
Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease
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DOI：
10.1073/pnas.0706006104
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发表时间：
2007-12-04
影响因子：
11.1
通讯作者：
Eidelberg, David
中科院分区：
文献类型：
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作者：
Feigin, Andrew;Kaplitt, Michael G.;Eidelberg, David
帕金森病（PD）的特征在于异常代谢脑网络的表达升高，其通过临床有效治疗而降低。我们使用氟代脱氧葡萄糖（FDG）正电子发射断层扫描（PET），以确定运动改善的基础上，在12例PD患者接受单侧丘脑底核（HDN）输注的腺相关病毒载体表达谷氨酸脱羧酶（AAV-GAD）。基因治疗后，我们观察到显着减少丘脑代谢的手术侧，以及并发代谢增加同侧运动和运动前皮质区。基线时，PD患者中与运动和认知功能相关的代谢网络活性异常升高明显。运动相关网络的活动在手术后下降，并持续1年。这些网络变化与改善的临床残疾评级相关。相比之下，认知相关网络的活动在基因转移后没有改变。这表明，异常网络活动的调节是在单方面MAAV-GAD基因治疗后观察到的临床结果的基础。网络生物标志物可用作PD和其他神经退行性疾病实验疗法早期试验中的生理测定。
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.