Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease
Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease
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DOI：
10.1038/nm850
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发表时间：
2003-05-01
期刊：
影响因子：
82.9
通讯作者：
Heywood, P
中科院分区：
文献类型：
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作者：
Gill, SS;Patel, NK;Heywood, P
神经胶质细胞系来源的神经营养因子（GDNF）是一种有效的神经营养因子，在多种帕金森病的啮齿动物和灵长类动物模型中具有恢复作用，但从血液或脑脊液渗透到脑组织的能力有限。在1期安全性试验中，我们将GDNF直接输送到5名帕金森患者的壳核中。一根导管需要重新定位，降低GDNF浓度后磁共振图像的变化消失。一年后，无严重的临床副作用，统一帕金森病评定量表（UPDRS）的停药期运动评分改善39%，日常生活活动评分改善61%。药物引起的运动障碍减少了64%，并且在慢性GDNF输送过程中未观察到停药。正电子发射断层扫描（PET）显示，18个月后[F-18]多巴胺摄取的壳核多巴胺储存显著增加28%，表明GDNF对多巴胺功能有直接影响。这项研究需要仔细检查GDNF作为帕金森病的治疗方法。
Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with restorative effects in a wide variety of rodent and primate models of Parkinson disease, but penetration into brain tissue from either the blood or the cerebro-spinal fluid is limited. Here we delivered GDNF directly into the putamen of five Parkinson patients in a phase 1 safety trial. One catheter needed to be repositioned and there were changes in the magnetic resonance images that disappeared after lowering the concentration of GDNF. After one year, there were no serious clinical side effects, a 39% improvement in the off-medication motor sub-score of the Unified Parkinson's Disease Rating Scale (UPDRS) and a 61% improvement in the activities of daily living sub-score. Medication-induced dyskinesias were reduced by 64% and were not observed off medication during chronic GDNF delivery. Positron emission tomography (PET) scans of [F-18] dopamine uptake showed a significant 28% increase in putamen dopamine storage after 18 months, suggesting a direct effect of GDNF on dopamine function. This study warrants careful examination of GDNF as a treatment for Parkinson disease.