Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
J Neuromuscul Dis. 2020;7(3):315-322. doi: 10.3233/JND-200493.
Spinal muscular atrophy (SMA) is a neuromuscular disorder affecting young children. While pre-clinical models of SMA show small spleens, the same is not true in humans. Here, we show by doppler ultrasonography decreased splenic blood flow in Smn2B/- mice. Further, AAV9-SMN gene therapy does not rescue the distal ear and tail necrosis nor the spleen size in these mice, suggesting that the latter may be linked to a cardiovascular defect. Absence of smaller spleens in human patients is likely due to differences in presentation of defects in SMA between pre-clinical mouse models and human patients, particularly the susceptibility to cardiovascular issues.
脊髓性肌萎缩症(SMA)是一种影响幼儿的神经肌肉疾病。虽然 SMA 的临床前模型显示脾脏较小,但在人类中并非如此。在这里,我们通过多普勒超声显示 Smn2B/- 小鼠的脾脏血流减少。此外,AAV9-SMN 基因治疗不能挽救这些小鼠的远端耳朵和尾巴坏死,也不能挽救脾脏大小,这表明后者可能与心血管缺陷有关。人类患者中不存在较小的脾脏可能是由于临床前小鼠模型和人类患者中 SMA 缺陷的表现存在差异,特别是对心血管问题的易感性。