Therapeutical strategy of Spinal muscular atrophy by RNA virus vector delivery to human iPS-derived neural cells

脊髓性肌萎缩症(SMA)是一种遗传性神经肌肉疾病，可导致运动神经元变性。SMA是由于SMN1基因的纯合缺失或突变导致运动神经元(SMN)存活蛋白产生减少所致。然而，到目前为止，SMN蛋白缺乏是如何导致SMA中选择性脊髓运动神经元死亡的尚不清楚，因为缺乏一种通过适当的传递到脊髓来表达SMN蛋白的方法。因此，目前尚不存在治疗SMA的有效方法。本研究旨在探讨基于脊灰病毒(PV)的嗜神经RNA病毒载体作为一种新型的外源蛋白治疗载体在人iPS来源的神经细胞和SMA来源的神经细胞中的潜力。

Spinal muscular atrophy (SMA), a genetic neuromuscular disorder, leads to motor neuron degeneration. SMA is caused by reduced production of the survival of motor neuron (SMN) protein resulting from the homozygous deletion or mutation of the SMN1 gene. To date, however, it remains unclear how SMN protein deficiency causes the selective spinal motor neuron death seen in SMA because of a lack of a method to express SMN proteins by the appropriate delivery to the spinal cord. Therefore, an effective treatment of SMA does not presently exist. This study was focused on the potential of a neurotropic RNA virus, poliovirus (PV)-based vector as a novel therapeutic delivery system of exogenous protein in human iPS-derived neural cells and SMA-derived cells.In this study, PV-based expression vector delivery method exhibited an insight into the GFP or GFP-SMN protein expression during an early stage of human iPS-derived neural cells and SMA patient-derived cells.