Volume 29 Issue 9, September 2022

Cover Credit:Intravenous (IV) AAV-mediated gene replacement therapy is widely used for the treatment of children with the motor neuron disease Spinal Muscular Atrophy (SMA). While both IV and centrally-delivered routes of injection are being explored in clinical trials, the biodistribution of the AAV and subsequent effects on overall pathology were yet to be described in detail. The image shows diseased neuromuscular junctions (NMJs) in the transversus abdominis muscle from a mouse model of SMA, where neurons are stained in green and motor endplates are stained in red. While centrally-delivered AAV9-SMN provides better neuronal and NMJ protection than IV delivery, both treatments result in a robust rescue of survival, weight, and motor function. These results emphasized the independent contributions of peripheral organs to SMA pathology.