Statins accelerate disease progression and shorten survival in SOD1(G93A) mice

Muscle Nerve. 2016 Aug;54(2):284-91. doi: 10.1002/mus.25048. Epub 2016 May 19.


Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: H63D HFE polymorphism; HMG-CoA reductase inhibitor; SOD1G93A; amyotrophic lateral sclerosis; coenzyme Q10; survival.

MeSH terms

  • Amyotrophic Lateral Sclerosis / chemically induced*
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / mortality
  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Extremities / physiopathology
  • Ferritins / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Male
  • Mice
  • Mice, Transgenic
  • Mitochondria / metabolism
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Muscle Strength / drug effects
  • Muscle Strength / genetics
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / ultrastructure
  • ROC Curve
  • Spinal Cord / ultrastructure
  • Superoxide Dismutase / genetics*
  • Ubiquinone / analogs & derivatives
  • Ubiquinone / pharmacology


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Ubiquinone
  • Ferritins
  • SOD1 G37R protein, mouse
  • Superoxide Dismutase
  • coenzyme Q10