Abnormal fatty acid metabolism is a core component of spinal muscular atrophy

Marc-Olivier Deguise, Giovanni Baranello, Chiara Mastella, Ariane Beauvais, Jean Michaud, Alessandro Leone, Ramona De Amicis, Alberto Battezzati, Christopher Dunham, Kathryn Selby, Jodi Warman Chardon, Hugh J McMillan, Yu-Ting Huang, Natalie L Courtney, Alannah J Mole, Sabrina Kubinski, Peter Claus, Lyndsay M Murray, Melissa Bowerman, Thomas H GillingwaterSimona Bertoli, Simon H Parson, Rashmi Kothary

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

OBJECTIVE: Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder leading to paralysis and subsequent death in young children. Initially considered a motor neuron disease, extra-neuronal involvement is increasingly recognized. The primary goal of this study was to investigate alterations in lipid metabolism in SMA patients and mouse models of the disease.

METHODS: We analyzed clinical data collected from a large cohort of pediatric SMA type I-III patients as well as SMA type I liver necropsy data. In parallel, we performed histology, lipid analysis, and transcript profiling in mouse models of SMA.

RESULTS: We identify an increased susceptibility to developing dyslipidemia in a cohort of 72 SMA patients and liver steatosis in pathological samples. Similarly, fatty acid metabolic abnormalities were present in all SMA mouse models studied. Specifically, Smn2B/- mice displayed elevated hepatic triglycerides and dyslipidemia, resembling non-alcoholic fatty liver disease (NAFLD). Interestingly, this phenotype appeared prior to denervation.

INTERPRETATION: This work highlights metabolic abnormalities as an important feature of SMA, suggesting implementation of nutritional and screening guidelines in patients, as such defects are likely to increase metabolic distress and cardiovascular risk. This study emphasizes the need for a systemic therapeutic approach to ensure maximal benefits for all SMA patients throughout their life.

Original languageEnglish
Pages (from-to)1519-1532
Number of pages14
JournalAnnals of Clinical and Translational Neurology
Issue number8
Early online date26 Jul 2019
Publication statusPublished - 11 Aug 2019


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