6 Citations (Scopus)

Abstract

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 SOD1G93A 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.

Original languageEnglish (US)
Pages (from-to)284-291
Number of pages8
JournalMuscle and Nerve
Volume54
Issue number2
DOIs
StatePublished - Aug 1 2016

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Disease Progression
coenzyme Q10
Simvastatin
Amyotrophic Lateral Sclerosis
Survival
Genotype
Muscles
Mitochondrial Proteins
Hand Strength
Mitochondria
Skeletal Muscle
Spine
Phenotype

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

Cite this

Su, Xiaowei W. ; Nandar, Wint ; Neely, Elizabeth B. ; Simmons, Zachary ; Connor, James R. / Statins accelerate disease progression and shorten survival in SOD1G93A mice. In: Muscle and Nerve. 2016 ; Vol. 54, No. 2. pp. 284-291.
@article{9fa622debace474fbdb6101788b5eda5,
title = "Statins accelerate disease progression and shorten survival in SOD1G93A mice",
abstract = "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 SOD1G93A 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.",
author = "Su, {Xiaowei W.} and Wint Nandar and Neely, {Elizabeth B.} and Zachary Simmons and Connor, {James R.}",
year = "2016",
month = "8",
day = "1",
doi = "10.1002/mus.25048",
language = "English (US)",
volume = "54",
pages = "284--291",
journal = "Muscle and Nerve",
issn = "0148-639X",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

Statins accelerate disease progression and shorten survival in SOD1G93A mice. / Su, Xiaowei W.; Nandar, Wint; Neely, Elizabeth B.; Simmons, Zachary; Connor, James R.

In: Muscle and Nerve, Vol. 54, No. 2, 01.08.2016, p. 284-291.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Statins accelerate disease progression and shorten survival in SOD1G93A mice

AU - Su, Xiaowei W.

AU - Nandar, Wint

AU - Neely, Elizabeth B.

AU - Simmons, Zachary

AU - Connor, James R.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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 SOD1G93A 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.

AB - 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 SOD1G93A 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.

UR - http://www.scopus.com/inward/record.url?scp=84978880175&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978880175&partnerID=8YFLogxK

U2 - 10.1002/mus.25048

DO - 10.1002/mus.25048

M3 - Article

C2 - 26799243

AN - SCOPUS:84978880175

VL - 54

SP - 284

EP - 291

JO - Muscle and Nerve

JF - Muscle and Nerve

SN - 0148-639X

IS - 2

ER -