在肌萎缩侧索硬化症的SOD1G93A模型中，腺相关病毒介导的胰岛素样生长因子-1脊髓实质内递送具有保护作用。
Intraparenchymal spinal cord delivery of adeno-associated virus IGF-1 is protective in the SOD1G93A model of ALS.
作者信息
Lepore Angelo C, Haenggeli Christine, Gasmi Mehdi, Bishop Kathie M, Bartus Raymond T, Maragakis Nicholas J, Rothstein Jeffrey D
机构信息
Department of Neurology, The Johns Hopkins University School of Medicine, 600 N. Wolfe St., Meyer 6-109, Baltimore, MD 21287, USA.
出版信息
Brain Res. 2007 Dec 14;1185:256-65. doi: 10.1016/j.brainres.2007.09.034. Epub 2007 Sep 22.
Abstract
The potent neuroprotective activities of neurotrophic factors, including insulin-like growth factor 1 (IGF-1), make them promising candidates for treatment of amyotrophic lateral sclerosis (ALS). In an effort to maximize rate of motor neuron transduction, achieve high levels of spinal IGF-1 and thus enhance therapeutic benefit, we injected an adeno-associated virus 2 (AAV2)-based vector encoding human IGF-1 (CERE-130) into lumbar spinal cord parenchyma of SOD1(G93A) mice. We observed robust and long-term intraspinal IGF-1 expression and partial rescue of lumbar spinal cord motor neurons, as well as sex-specific delayed disease onset, weight loss, decline in hindlimb grip strength and increased animal survival.
摘要
神经营养因子具有强大的神经保护活性，包括胰岛素样生长因子1（IGF-1），这使其成为治疗肌萎缩侧索硬化症（ALS）的有前景的候选药物。为了最大限度地提高运动神经元转导率，实现脊髓中高水平的IGF-1从而增强治疗效果，我们将一种基于腺相关病毒2（AAV2）的编码人IGF-1的载体（CERE-130）注射到SOD1（G93A）小鼠的腰段脊髓实质中。我们观察到脊髓内IGF-1的强劲且长期表达以及腰段脊髓运动神经元的部分挽救，还有性别特异性的疾病发作延迟、体重减轻、后肢握力下降以及动物存活率提高。
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