spinal muscular atrophy (sma) is a neurodegenerative disease caused by the loss of survival motor neuron-1 (smn1). in all sma patients, a nearly identical copy gene called smn2 is present, which produces low levels of functional protein owing to an alternative splicing event. to prevent exon-skipping, we h脊肌萎缩侧索硬化症ave targeted an intronic repressor, element1 (e1), located upstream of smn2 exon 7 using morpholino-based antisense oligonucleotides (e1mo-asos). a single intracerebroventricular injection in the relatively severe mouse model of sma (smnδ7 mouse model) elicited a robust induction of smn protein, and mean life s治疗肌萎缩医院排名pan was extended from an average survival of 13 to 54 days following a single dose, consistent with large weight gains and a correction of the neuronal pathology. additionally, e1mo-aso treatment in an intermediate sma mouse (smnrt mouse model) significantly extended life span by ∼700% and weight gain was comp面肌萎缩arable with the unaffected animals. while a number of experimental therapeutics have targeted the iss-n1 element of smn2 pre-mrna, the development of e1 asos provides a new molecular target for sma therapeutics that dramatically extends survival in two important pre-clinical models of disease.

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通过对小抗肌萎缩侧索硬化症鼠进行研究,研究者发现,靶向药物可以改善小鼠的生存率,高达500%至700%,而且对脊髓性肌萎缩症的改善率也高达90%

文章中,研究者chris lorson表示,我们的策略就是利用抑制子来抵御脊髓性肌萎缩症,文章中我们发现反义的寡核苷酸可以有效修复影响脊髓性肌萎缩症疾病的基因的表达,其或许可以作为抵御脊髓性肌萎缩症的疗法,

在脊髓性肌萎缩症患者机体中,脊髓运动神经元-1(smn-1)处于突变状态,而且其缺少一种帮助恢复肌肉神经元功能的蛋白质,不幸的是人类存在同样拷贝的基因smn-2,因此研究者就将以该基因的特殊遗传序列为靶点来该基因,从而帮助恢复肌肉神经元的功能

2014年9月18日 讯 /生物谷bioon/ --有研究表明,每40个美国人就有1人治疗肌萎缩的药是脊髓性肌萎缩易感基因的携带者,近日,来自密苏里大学的研究人员通过研究开发了一种新型化合物,其可以对患脊髓性肌萎缩的动物模型进行有效治疗,相关研究刊登于国际杂志human molecular genetics上尽管当前并没有脊髓性肌萎缩症的有效疗法,但是研究者在研究脊髓性肌萎缩症的路上又迈进了一大步,相关研究由美国国立卫生研究院提供资助(生物谷bioon.com)

doi:10.1093/hmg/ddu198

morpholino antisense oligonucleotides targeting intronic repressor element1 improve phenotype in sma mouse 小儿脊髓性肌萎缩models

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erkan y. osman1,2, madeline r. miller2,3, kate l. robbins2, abby m. lombardi2, arleigh k. atkinson2, amanda j. brehm4 and christian l. lorson1,2,3,*

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