Spinal muscular atrophy: an update on therapeutic progress.
Spinal muscular atrophy: an update on therapeutic progress.
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脊髓性肌萎缩症：治疗进展的最新进展。
DOI：
10.1016/j.bbadis.2013.08.005
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Singh,RavindraN
中科院分区：
文献类型：
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作者：
Seo,Joonbae;Howell,MatthewD;Singh,NataliaN;Singh,RavindraN
人类有两个几乎相同的运动神经元存活基因：SMN1和SMN2。SMN1的缺失或突变与SMN2无法补偿SMN1的缺失相结合导致脊髓性肌萎缩症（SMA），这是婴儿死亡的主要遗传原因。SMA影响约6000例活产婴儿中的1例，其频率远高于几种遗传疾病。SMN2的主要已知缺陷是主要外显子7跳跃，导致产生不稳定的截短蛋白（SMNΔ7）。因此，SMA已成为一种模型遗传性疾病，几乎整个疾病人群都可能与单个外显子（即SMN2外显子7）的异常剪接有关。已经设想了旨在改善SMN 2功能的多种治疗策略。这些策略包括但不限于操纵转录、纠正异常剪接和稳定mRNA、SMN和SMN Δ7。本文综述了SMA治疗的各种体内研究的最新进展和前景。
Humans have two nearly identical copies of survival motor neuron gene:SMN1andSMN2. Deletion or mutation ofSMN1combined with the inability ofSMN2to compensate for the loss ofSMN1results in spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. SMA affects 1 in ~ 6000 live births, a frequency much higher than in several genetic diseases. The major known defect ofSMN2is the predominant exon 7 skipping that leads to production of a truncated protein (SMNΔ7), which is unstable. Therefore, SMA has emerged as a model genetic disorder in which almost the entire disease population could be linked to the aberrant splicing of a single exon (i.e.SMN2exon 7). Diverse treatment strategies aimed at improving the function ofSMN2have been envisioned. These strategies include, but are not limited to, manipulation of transcription, correction of aberrant splicing and stabilization of mRNA,SMNandSMNΔ7. This review summarizes up to date progress and promise of various in vivo studies reported for the treatment of SMA.