Liver SMN restoration rescues the Smn mouse model of spinal muscular atrophy
Emma R Sutton, Ariane Beauvais, Rebecca Yaworski, Yves De Repentigny, Aoife Reilly, Monique Marylin Alves de Almeida, Marc‐Olivier Deguise, Kathy L. Poulin, Robin J. Parks, Bernard L. Schneider, Rashmi Kothary
Abstract
BACKGROUND: The liver is a key metabolic organ, acting as a hub to metabolically connect various tissues. Spinal muscular atrophy (SMA) is a neuromuscular disorder whereby patients have an increased susceptibility to developing dyslipidaemia and liver steatosis. It remains unknown whether fatty liver is due to an intrinsic or extrinsic impact of survival motor neuron (SMN) protein depletion. METHODS: mice, a model of SMA. Experiments assessed central and peripheral impacts using immunoblot, immunohistochemistry, and electron microscopy techniques. FINDINGS: mice. Fatty liver was ameliorated while key markers of liver function were also restored to normal levels. Certain peripheral pathologies were rescued including muscle size and pancreatic cell imbalance. Only a partial CNS recovery was seen using a liver therapeutic strategy alone. INTERPRETATION: mice. FUNDING: This work was funded by Muscular Dystrophy Association (USA) [grant number 963652 to R.K.]; the Canadian Institutes of Health Research [grant number PJT-186300 to R.K.].