Abstract | 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: 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.
|
Authors | 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 Gillingwater, Simona Bertoli, Simon H Parson, Rashmi Kothary |
Journal | Annals of clinical and translational neurology
(Ann Clin Transl Neurol)
Vol. 6
Issue 8
Pg. 1519-1532
(08 2019)
ISSN: 2328-9503 [Electronic] United States |
PMID | 31402618
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Copyright | © 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. |
Chemical References |
- Fatty Acids
- Survival of Motor Neuron 1 Protein
- Triglycerides
|
Topics |
- Animals
- Child
- Child, Preschool
- Disease Models, Animal
- Dyslipidemias
(etiology, genetics, metabolism)
- Fatty Acids
(genetics, metabolism)
- Fatty Liver
(etiology, genetics, metabolism)
- Female
- Humans
- Infant
- Lipid Metabolism
(genetics)
- Male
- Mice
- Mice, Transgenic
- Muscular Atrophy, Spinal
(complications, genetics, metabolism)
- Survival of Motor Neuron 1 Protein
(genetics)
- Triglycerides
(metabolism)
|