NsGene A/S, Ballerup, Denmark.
Restor Neurol Neurosci. 2012;30(3):225-36. doi: 10.3233/RNN-2012-110199.
Encapsulated cell (EC) biodelivery is a promising, clinically relevant technology platform to safely target the delivery of therapeutic proteins to the central nervous system. The purpose of this study was to evaluate EC biodelivery of the novel neurotrophic factor, Meteorin, to the striatum of rats and to investigate its neuroprotective effects against quinolinic acid (QA)-induced excitotoxicity.
Meteorin-producing ARPE-19 cells were loaded into EC biodelivery devices and implanted into the striatum of rats. Two weeks after implantation, QA was injected into the ipsilateral striatum followed by assessment of neurological performance two and four weeks after QA administration.
Implant-delivered Meteorin effectively protected against QA-induced toxicity, as manifested by both near-normal neurological performance and reduction of brain cell death. Morphological analysis of the Meteorin-treated brains showed a markedly reduced striatal lesion size. The EC biodelivery devices produced stable or even increasing levels of Meteorin throughout the study over 6 weeks.
Stereotactically implanted EC biodelivery devices releasing Meteorin could offer a feasible strategy in the treatment of neurological diseases with an excitotoxic component such as Huntington's disease. In a broader sense, the EC biodelivery technology is a promising therapeutic protein delivery platform for the treatment of a wide range of diseases of the central nervous system.
包裹细胞（EC）递药是一种很有前途的、与临床相关的技术平台，可安全地将治疗性蛋白递送到中枢神经系统。本研究的目的是评估新型神经营养因子 Meteorin 通过 EC 递药递送至大鼠纹状体，并研究其对喹啉酸（QA）诱导的兴奋性毒性的神经保护作用。
将产生 Meteorin 的 ARPE-19 细胞装入 EC 递药装置中，并植入大鼠纹状体。植入 2 周后，将 QA 注射到同侧纹状体，然后在 QA 给药后 2 周和 4 周评估神经功能表现。
植入的 Meteorin 可有效抵抗 QA 诱导的毒性，表现在神经功能几乎正常和减少脑细胞死亡。对 Meteorin 处理的大脑进行形态学分析显示纹状体损伤明显缩小。在整个 6 周的研究过程中，EC 递药装置稳定甚至持续释放 Meteorin。
通过立体定向植入的 EC 递药装置释放 Meteorin 可能为治疗具有兴奋性毒性的神经疾病（如亨廷顿病）提供一种可行的策略。更广泛地说，EC 递药技术是一种很有前途的治疗性蛋白递药平台，可用于治疗中枢神经系统的广泛疾病。
