AAV2 - mediated delivery of human neurturin to the rat nigrostriatal system: Long-term efficacy and tolerability of CERE-120 for Parkinson's disease
AAV2 - mediated delivery of human neurturin to the rat nigrostriatal system: Long-term efficacy and tolerability of CERE-120 for Parkinson's disease
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DOI：
10.1016/j.nbd.2007.04.003
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发表时间：
2007-07-01
影响因子：
6.1
通讯作者：
Bartus, Raymond T.
中科院分区：
文献类型：
--
作者：
Gasmi, Mehdi;Brandon, Eugene P.;Bartus, Raymond T.
Neurturin(NTN)是一种神经营养因子，具有保护和恢复黑质多巴胺能神经元的功能，其变性与帕金森病(PD)的主要运动障碍关系最为密切。CERE-120是一种基于腺相关病毒2型(AAV2)的编码人NTN的基因递送载体，正被开发为一种潜在的帕金森病治疗方法。在本文报道的一系列临床前研究中，CERE-I纹状体给药对大鼠6-羟基多巴胺(6-OHDA)损伤模型的黑质纹状体神经元产生了剂量相关的神经保护作用。CERE-120的长期疗效体现在黑质细胞的保护、纹状体纤维神经的保存和至少6个月的行为恢复。此外，在治疗后至少12个月内，纹状体注射CERE-120被发现具有安全性和耐受性，没有副作用或毒理学反应，即使剂量是测试的最低有效剂量的125倍。这些结果支持正在进行的针对帕金森病患者的CERE-120临床计划。(C)2007年，爱思唯尔公司出版。
Neurturin (NTN) is a neurotrophic factor with known potential to protect and restore the function of dopaminergic substantia nigra neurons whose degeneration has been most closely linked to the major motor deficits in Parkinson's disease (PD). CERE-120, an adeno-associated virus serotype 2 (AAV2)-based gene delivery vector encoding human NTN, is being developed as a potential therapeutic for PD. In a series of preclinical studies reported herein, CERE-I delivery to the striatum produced a dose-related neuroprotection of nigrostriatal neurons in the rat 6-hydroxydopamine (6-OHDA) lesion model. Long-lasting efficacy of CERE-120 was evidenced by substantia nigra cell protection, preserved fiber innervation of the striatum, and behavioral recovery for at least 6 months. In addition, striatal infusion of CERE-120 was found to have a safety and tolerability profile devoid of side effects or toxicological responses, for at least 12 months post-treatment, even at dose multiples 125 times that of the lowest efficacious dose tested. These results support the ongoing CERE-120 clinical program in PD patients. (c) 2007 Published by Elsevier Inc.