Kliem Michele A, Heeke Brenten L, Franz Colin K, Radovitskiy Igor, Raore Bethwel, Barrow Emily, Snyder Brooke R, Federici Thais, Kaye Spratt S, Boulis Nicholas M
Department of Neurosurgery , Emory University, Atlanta , Georgia, USA.
Amyotroph Lateral Scler. 2011 Sep;12(5):331-9. doi: 10.3109/17482968.2011.574142. Epub 2011 Aug 24.
Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron loss leading to paralysis and death. Vascular endothelial growth factor (VEGF) has angiogenic, neurotrophic, and neuroprotective properties, and has preserved neuromuscular function and protected motor neurons in rats engineered to overexpress the human gene coding the mutated G93A form of the superoxide dismutase-1 (SOD1). We assessed the effects of intramuscular administration of a plasmid that encodes a zinc finger protein transcription factor (ZFP-TF) engineered to induce VEGF expression in the SOD1 rat model of ALS. Weekly injections of the plasmid preserved ipsilateral hindlimb grip strength and markedly improved rotarod performance in SOD1 rats compared to the vehicle-treated group. The number of motor neurons and the proportion of innervated neuromuscular junctions were similar in both groups. In conclusion, our data suggest that administration of the VEGF-ZFP-TF may be neuroprotective and has potential as a safe and practical approach for the management of motor disability in ALS.
肌萎缩侧索硬化症（ALS）的特征是运动神经元丧失，最终导致瘫痪和死亡。血管内皮生长因子（VEGF）具有血管生成、神经营养和神经保护特性，在经过基因工程改造以过度表达编码突变型G93A形式超氧化物歧化酶-1（SOD1）的人类基因的大鼠中，VEGF可维持神经肌肉功能并保护运动神经元。我们评估了在ALS的SOD1大鼠模型中，肌肉注射一种编码锌指蛋白转录因子（ZFP-TF）的质粒的效果，该转录因子经基因工程改造可诱导VEGF表达。与载体处理组相比，每周注射该质粒可维持SOD1大鼠同侧后肢握力，并显著改善其转棒试验表现。两组的运动神经元数量和神经支配的神经肌肉接头比例相似。总之，我们的数据表明，给予VEGF-ZFP-TF可能具有神经保护作用，并且作为一种安全实用的方法来管理ALS中的运动功能障碍具有潜力。
