Affiliations: [a] Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| [b] Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
| [c] Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada
| [d] Bertarelli Foundation Gene Therapy Platform, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1202 Geneva, Switzerland
Brain Mind Institute, 27218 Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| [f] Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, and Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
Abstract: 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.