Are statin medications safe in patients with ALS?

Zinman, Lorne; Sadeghi, Reza; Gawel, Marek; Patton, Dan; Kiss, Alex

doi:10.1080/17482960802031092

Cited by 69 publications

(44 citation statements)

References 22 publications

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“…Since then, the association between statins and ALS has become controversial. A recent study reported a strong association between statin medications and more rapid ALS progression, although the study was performed in only a small number of patients with the disease [9]. In contrast, a retrospective investigation of a large number of patients with ALS did not find any influence of statins on survival, concluding that statin treatments are safe for patients with ALS [10].…”

Section: Introductionmentioning

confidence: 96%

Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging

Lee

Choi

et al. 2015

Mol Neurobiol

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Although statins, or hydroxymethylglutaryl coenzyme A (HMG-Co A) reductase inhibitors, are generally used to decrease levels of circulating cholesterol, they have also been reported to have neuroprotective effects through various mechanisms. However, recent results have indicated that they may be harmful in patients with amyotrophic lateral sclerosis (ALS). In this study, we investigate whether atorvastatin protects motor neuron-like cells (NSC-34D) from oxidative stress. To evaluate the effects of atorvastatin or hydrogen peroxide or both on NSC-34D cells, the cells were treated with various combinations of these agents. To evaluate the viability of the cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and trypan blue staining were performed. Levels of free radicals and intracellular signaling proteins were evaluated using the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and Western blotting, respectively. Atorvastatin protected NSC-34D cells against oxidative stress in a concentration-dependent manner. This neuroprotective effect of atorvastatin was blocked by LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor and by FR180204, a selective extracellular signal-related kinase (ERK) inhibitor. Atorvastatin treatment increased the expression levels of p85αPI3K, phosphorylated Akt, phosphorylated glycogen synthase kinase-3β, phosphorylated ERK, and Bcl-2, which are proteins related to survival. Furthermore, atorvastatin decreased the levels of cytosolic cytochrome C, Bax, cleaved caspase-9, and cleaved caspase-3, which are associated with death in oxidative stress-injured NSC-34D cells. We conclude that atorvastatin has a protective effect against oxidative stress in motor neurons by activating the PI3K and ERK pathways as well as by scavenging free radicals. These findings indicate that statins could help protect motor neurons from oxidative stress.

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Section: Introductionmentioning

confidence: 96%

Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging

Lee

Choi

et al. 2015

Mol Neurobiol

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“…A recent study [3] reported a strong association between statin medications and a more rapid rate of functional decline in small numbers of patients with ALS, leading those authors to advise exercising caution and discussing discontinuation or replacement of statin medications. In contrast, a large study whose information was retrieved from the database of several completed clinical trials found no indication of any impact of statins on the ALS disease course [4].…”

Section: Introductionmentioning

confidence: 99%

Gender-based effect of statins on functional decline in amyotrophic lateral sclerosis

Hirsch

Cudkowicz

Drory

2011

Journal of the Neurological Sciences

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“…Dyslipidemia is associated to prolonged survival, and lipid-lowering drugs should be discontinued. 33,34 Statins have also been related to potential worsening of symptoms in myasthenia gravis. 23 In recent years, genetic factors have been increasingly thought to influence individual risk of statin-related myotoxicity.…”

Section: Individual Factorsmentioning

confidence: 99%

Statin-related myotoxicity

Fernandes

Santos

Pérez

2016

Endocrinología y Nutrición

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Statin therapy has a very important role in decreasing cardiovascular risk, and treatment non-compliance may therefore be a concern in high cardiovascular risk patients. Myotoxicity is a frequent side effect of statin therapy and one of the main causes of statin discontinuation, which limits effective treatment of patients at risk of or with cardiovascular disease. Because of the high proportion of patients on statin treatment and the frequency of statinrelated myotoxicity, this is a subject of concern in clinical practice. However, statin-related myotoxicity is probably underestimated because there is not a gold standard definition, and its diagnosis is challenging. Moreover, information about pathophysiology and optimal therapeutic options is scarce. Therefore, this paper reviews the knowledge about the definition, pathophysiology and predisposing conditions, diagnosis and management of statin-related myotoxicity, and provides a practical scheme for its management in clinical practice. © 2016 SEEN. Published by Elsevier España, S.L.U. All rights reserved. PALABRAS CLAVEEstatinas; Inhibidores de la HMG-CoA reductasa; Efectos secundarios a fármacos; Intolerancia a estatinas; Miotoxicidad; Miopatía Miotoxicidad por estatinasResumen El tratamiento con estatinas tiene un papel fundamental en la reducción del riesgo cardiovascular, y la falta de adherencia al mismo es motivo de preocupación en los pacientes con alto riesgo. La miotoxicidad es un efecto secundario frecuente y una de las principales causas de interrupción de las estatinas, lo que limita el tratamiento eficaz de los pacientes con riesgo de enfermedad cardiovascular. Considerando la elevada proporción de pacientes en tratamiento con estatinas, y la frecuencia de miotoxicidad asociada, este es un tema relevante en la práctica clínica. Sin embargo, la miotoxicidad por las estatinas está probablemente subestimada debido a que no hay una definición bien establecida y su diagnóstico resulta difícil. * Corresponding author. E-mail address: aperez@santpau.cat (A. Pérez). 1 The first two authors contributed equally to this work. þÿ D e s c a r g a d o d e C l i n i c a l K e y . e s d e s d e F u n d a c i ó d e G e s t i ó S a n i t à r i a d e l H o s p i t a l d e S a n t a C r e u i S a n t P a u m a y o 0 8 , 2 0 1 6 . Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2016. Elsevier Inc. Todos los derechos reservados. V. Fernandes et al.Además, la información sobre la fisiopatología y las opciones terapéuticas óptimas es escasa. En este artículo revisamos la definición, fisiopatología y condiciones predisponentes, diagnóstico y tratamiento de la miotoxicidad por las estatinas, y proponemos un esquema práctico para su manejo.

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Are statin medications safe in patients with ALS?

Cited by 69 publications

References 22 publications

Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging

Atorvastatin Protects NSC-34 Motor Neurons Against Oxidative Stress by Activating PI3K, ERK and Free Radical Scavenging

Gender-based effect of statins on functional decline in amyotrophic lateral sclerosis

Statin-related myotoxicity

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