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

Muscle & Nerve
Xiaowei W SuJames R Connor

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.

References

Mar 1, 1989·Trends in Neurosciences·M T Wong-Riley
Jan 1, 1997·Molecular Aspects of Medicine·S A MortensenM Rohde
Mar 27, 2001·Current Opinion in Lipidology·J M Dietschy, S D Turley
Aug 28, 2001·The American Journal of Clinical Nutrition·J C DesportP Couratier
Jul 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Luc DupuisJean-Philippe Loeffler
Nov 18, 2004·Journal of the Neurological Sciences·Xin-Sheng WangJames Connor
Jan 7, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ilias G KirkinezosCarlos T Moraes
May 4, 2006·Muscle & Nerve·Georgirene D VladutiuPaul S Phillips
Aug 16, 2006·Neuro-degenerative Diseases·Jean-Claude DesportPhilippe Couratier
Jan 11, 2007·Archives of Neurology·Nadia A SutedjaLeonard H Van den Berg
Feb 20, 2007·Journal of Neurology, Neurosurgery, and Psychiatry·G RestagnoA Chiò
Apr 18, 2007·Journal of Lipid Research·Anissa FerganiJean-Philippe Loeffler
Jun 7, 2007·Journal of Neurology, Neurosurgery, and Psychiatry·S ZoccolellaUNKNOWN SLAP Registry
Sep 11, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christina EllervikBørge G Nordestgaard
Jul 9, 2008·Amyotrophic Lateral Sclerosis : Official Publication of the World Federation of Neurology Research Group on Motor Neuron Diseases·Lorne ZinmanAlex Kiss
Aug 5, 2008·Journal of Neurology·E F GoodallK E Morrison
Aug 6, 2008·Journal of the Neurological Sciences·Vivian E DroryBeatrice Nefussy
Dec 9, 2008·The Biochemical Journal·Michael P Murphy
Jan 23, 2009·American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions·Beatrice A Golomb, Marcella A Evans
Apr 8, 2009·The American Journal of Pathology·Veronique E MironJack P Antel
Jan 1, 2008·The Open Neurology Journal·Muddasir QureshiMerit E Cudkowicz
Jun 1, 2010·Toxicology·Amr A FouadMohamed T Yacoubi
Jun 10, 2010·Circulation. Cardiovascular Quality and Outcomes·Henrik Toft SørensenLars Pedersen
Jul 21, 2010·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·X HeY Xu
Nov 9, 2010·Journal of the Neurological Sciences·Beatrice NefussyVivian E Drory
Feb 25, 2011·The Journal of Nutrition·Wint Nandar, James R Connor
Mar 20, 2012·Journal of the Neurological Sciences·Julien PralineUNKNOWN French ALS Study Group
Jun 19, 2012·BMC Musculoskeletal Disorders·Beth B MurinsonNicholas J Maragakis
Oct 16, 2012·Neurobiology of Aging·Wouter van RheenenLeonard H van den Berg
Nov 9, 2012·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Zhenzhen ZhengHuifang Shang
Feb 16, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tilman VoigtAnnette Draeger
Dec 20, 2013·Circulation·Alan S GoUNKNOWN American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Jan 21, 2014·Neurobiology of Aging·Fatima Ali-RahmaniCara-Lynne Schengrund
Jan 22, 2014·Circulation·Alan S GoUNKNOWN American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Mar 22, 2014·The New England Journal of Medicine·Michael J PencinaEric D Peterson
Jul 26, 2014·Journal of Neurology·Meinie SeelenLeonard H van den Berg

❮ Previous
Next ❯

Citations

Apr 12, 2017·Current Environmental Health Reports·Jordan M BaileyWilliam D Atchison
Feb 11, 2018·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Beatrice A GolombKeith B Hoffman
Feb 26, 2020·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·D MariosaF Fang
Oct 16, 2018·Expert Opinion on Drug Discovery·Alexander McGown, Matthew John Stopford
May 22, 2019·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·D Michal FreedmanRuth M Pfeiffer
Oct 27, 2020·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Beata ChełstowskaMagdalena Kuźma-Kozakiewicz
Jul 30, 2021·Acta neurologica Belgica·Fardin NabizadehAbdorreza Naser Moghadasi

❮ Previous
Next ❯

Related Concepts

Related Feeds

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

ALS: Phenotypes

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder characterized phenotypically by progressive muscle weakness. Clinical phenotypes of ALS can be classified based on the pattern, level, and area of onset (e.g. bulbar, cervical, lumbar). Here is the latest research investigating phenotypes of ALS.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.