SMN1 and nutritional deficiency disease: ASO-induced SMN deficiency may trigger a further decrease in SMN2 splicing through a feedback loop (Jodelka et al, 2010; Ruggiu et al, 2012), on top of which, end-stage-disease conditions, such as nutritional deficiency and hypoxia may cause widespread splicing alterations, including in SMN2 (Bebee et al, 2012; Sahashi et al, 2012), each of which may potentially accelerate SMA progression.