title: Statins accelerate disease progression and shorten survival in SOD1(G93A) mice.
abstract: HMG-CoA reductase inhibitors (statins) and H63D HFE polymorphism may modify amyotrophic lateral sclerosis (ALS). We hypothesized that statins worsen phenotype in ALS mice, dependent on HFE genotype.
  
  
  
  Mice harboring SOD1(G93A) heterozygous for H67D Hfe (homologous to human H63D HFE) were administered simvastatin and/or coenzyme Q10, and were allowed to reach end stage. Disease progression was measured by grip strength. A separate group of animals was administered simvastatin and euthanized at the symptomatic 120-day time-point. Mitochondria from gastrocnemius muscle and lumbar spine were analyzed.
  
  
  
  Simvastatin and H67D Hfe accelerated disease progression. Simvastatin decreased survival. Coenzyme Q10 did not rescue statin-induced effects. Statins did not alter mitochondrial protein levels.
  
  
  
  Statins and Hfe genotype alter disease course in the ALS mouse model. Because the H63D HFE polymorphism is present in 30% of patients with ALS, studying disease progression in patients who receive statins, stratified for HFE genotype, may guide therapy. Muscle Nerve, 2016 Muscle Nerve 54: 284-291, 2016.
authors.affiliation: Department of Neurosurgery, Penn State College of Medicine, Mailcode H110, 500 University Drive, Hershey, Pennsylvania, 17033, USA.
authors.forename: Xiaowei W
authors.identifier: 0000-0002-1589-6570
authors.initials: XW
authors.lastname: Su
authors.affiliation: Department of Neurosurgery, Penn State College of Medicine, Mailcode H110, 500 University Drive, Hershey, Pennsylvania, 17033, USA.
authors.forename: Wint
authors.initials: W
authors.lastname: Nandar
authors.affiliation: Department of Neurosurgery, Penn State College of Medicine, Mailcode H110, 500 University Drive, Hershey, Pennsylvania, 17033, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Neely
authors.affiliation: Department of Neurology, Penn State College of Medicine, Hershey, Pennsylvania, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Simmons
authors.affiliation: Department of Neurosurgery, Penn State College of Medicine, Mailcode H110, 500 University Drive, Hershey, Pennsylvania, 17033, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Connor
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000139:chemically induced* / Q000235:genetics* / Q000401:mortality; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D005121:Extremities / Q000503:physiopathology; D005293:Ferritins / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D053580:Muscle Strength / Q000187:drug effects / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D012372:ROC Curve; D013116:Spinal Cord / Q000648:ultrastructure; D013482:Superoxide Dismutase / Q000235:genetics*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014451:Ubiquinone; D005293:Ferritins; C470429:SOD1 G37R protein, mouse; D013482:Superoxide Dismutase; C024989:coenzyme Q10
keywords: H63D HFE polymorphism; HMG-CoA reductase inhibitor; SOD1G93A; amyotrophic lateral sclerosis; coenzyme Q10; survival