Departments of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Stockholm, Sweden. maria.eriksdotter.jonhagen @ ki.se
Dement Geriatr Cogn Disord. 2012;33(1):18-28. doi: 10.1159/000336051. Epub 2012 Feb 22.
BACKGROUND/AIMS: Degeneration of cholinergic neurons in the basal forebrain correlates with cognitive decline in patients with Alzheimer's disease (AD). Targeted delivery of exogenous nerve growth factor (NGF) has emerged as a potential AD therapy due to its regenerative effects on the basal forebrain cholinergic neurons in AD animal models. Here we report the results of a first-in-man study of encapsulated cell (EC) biodelivery of NGF to the basal forebrain of AD patients with the primary objective to explore safety and tolerability.
This was an open-label, 12-month study in 6 AD patients. Patients were implanted stereotactically with EC-NGF biodelivery devices targeting the basal forebrain. Patients were monitored with respect to safety, tolerability, disease progression and implant functionality.
All patients were implanted successfully with bilateral single or double implants without complications or signs of toxicity. No adverse events were related to NGF or the device. All patients completed the study, including removal of implants at 12 months. Positive findings in cognition, EEG and nicotinic receptor binding in 2 of 6 patients were detected.
This study demonstrates that surgical implantation and removal of EC-NGF biodelivery to the basal forebrain in AD patients is safe, well tolerated and feasible.
背景/目的：基底前脑胆碱能神经元的退化与阿尔茨海默病（AD）患者的认知能力下降相关。由于其对 AD 动物模型基底前脑胆碱能神经元的再生作用，靶向传递外源性神经生长因子（NGF）已成为一种潜在的 AD 治疗方法。在此，我们报告了首例在 AD 患者的基底前脑中使用封装细胞（EC）传递 NGF 的人体研究结果，主要目的是探索安全性和耐受性。
这是一项在 6 名 AD 患者中进行的开放性、12 个月的研究。患者通过立体定向手术将 EC-NGF 生物传递装置植入基底前脑。监测患者的安全性、耐受性、疾病进展和植入物功能。
所有患者均成功植入双侧单或双植入物，无并发症或毒性迹象。无与 NGF 或装置相关的不良事件。所有患者均完成了研究，包括在 12 个月时取出植入物。在 6 名患者中的 2 名中检测到认知、脑电图和烟碱受体结合的阳性发现。
这项研究表明，在 AD 患者中，将 EC-NGF 生物传递至基底前脑的手术植入和取出是安全、耐受良好且可行的。
