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

Hirsch, Jonathan; Cudkowicz, Merit; Drory, Vivian E.

doi:10.1016/j.jns.2010.10.011

Cited by 22 publications

(23 citation statements)

References 27 publications

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“…However, more rigorous analyses have subsequently found a null association between statins and ALS risk (OR: 0.96, 95% CI: 0.73–1.28, [ 158 ]), as well as, prognosis [ 45 ]. Similarly, other reports suggest that the association between statin use and risk of ALS could be gender-dependent, with only female ALS patients on statins showing a significantly faster decline (a decline of 3 points more over 12 months) in (ALS-functional rating scale) ALS-FRS compared to those not on statins [ 118 ].…”

Section: The Disease-modifying Effects Of Metabolic Disorders In Alsmentioning

confidence: 86%

Disease-modifying effects of metabolic perturbations in ALS/FTLD

Jawaid

Khan

Polymenidou

et al. 2018

Mol Neurodegeneration

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Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two fatal neurodegenerative disorders with considerable clinical, pathological and genetic overlap. Both disorders are characterized by the accumulation of pathological protein aggregates that contain a number of proteins, most notably TAR DNA binding protein 43 kDa (TDP-43). Surprisingly, recent clinical studies suggest that dyslipidemia, high body mass index, and type 2 diabetes mellitus are associated with better clinical outcomes in ALS. Moreover, ALS and FTLD patients have a significantly lower incidence of cardiovascular disease, supporting the idea that an unfavorable metabolic profile may be beneficial in ALS and FTLD. The two most widely studied ALS/FTLD models, super-oxide dismutase 1 (SOD1) and TAR DNA binding protein of 43 kDA (TDP-43), reveal metabolic dysfunction and a positive effect of metabolic strategies on disease onset and/or progression. In addition, molecular studies reveal a role for ALS/FTLD-associated proteins in the regulation of cellular and whole-body metabolism. Here, we systematically evaluate these observations and discuss how changes in cellular glucose/lipid metabolism may result in abnormal protein aggregations in ALS and FTLD, which may have important implications for new treatment strategies for ALS/FTLD and possibly other neurodegenerative conditions.

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Section: The Disease-modifying Effects Of Metabolic Disorders In Alsmentioning

confidence: 86%

Disease-modifying effects of metabolic perturbations in ALS/FTLD

Jawaid

Khan

Polymenidou

et al. 2018

Mol Neurodegeneration

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“…Some data suggest that there is no difference in survival for patients taking statins and those not taking statins (72); however, these data are not from a randomized controlled clinical trial. Other data suggest that statins may be associated with faster progression and that this association may be gender specific (73). It was suggested that in studies evaluating statins as a risk factor, data on lipid profiles should also be collected, although some small studies find no relationship between total cholesterol and ALS (74).…”

Section: Discussionmentioning

confidence: 99%

Current pathways for epidemiological research in amyotrophic lateral sclerosis

Factor-Litvak

Al‐Chalabi

Ascherio³

et al. 2013

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease. The current status of the epidemiology, challenges to its study, and novel study design options are discussed in this paper. We focus on recent results from large-scale population based prospective studies, case-control studies and population based registries, risk factors, and neuropathologic findings in chronic traumatic encephalomyelopathy. We identify areas of interest for future research, including time-trends in the incidence and prevalence of ALS; the meaning of lifetime risk; the phenotypic description of ALS; the definition of familial versus sporadic ALS, syndromic aspects of ALS; specific risk factors such as military service, life style factors such as smoking, the use of statins, and the presence of β-N-methylamino-L-alanine (BMAA), an excitotoxic amino acid derivative possibly produced by cyanobacteria found in almost every terrestrial and aquatic habitat; the emergence and disappearance of an endemic ALS in areas of the Pacific; and gene-environment interactions in the etiology of ALS. To move the epidemiology forward, we suggest using well-characterized cohorts of newly diagnosed ALS patients to identify risk and prognostic factors; storing biological material for future studies; building on the National ALS Registry as a resource of future studies; working in multidisciplinary consortia; and addressing the possible early life etiology of ALS.

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“…Considering strict gender balance in test and control groups, seprating it in different groups, blinding in treatment assignment and using randomization and concealment of allocation in preclinical studies. [38][39][40][41][42] 8. Using guidelines for preclinical studies vis-avis standard RCTS, for example Animals in Research:…”

mentioning

confidence: 99%

Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs

Jaiswal

2018

Medicinal Research Reviews

332

211

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Over the past decades, a multitude of experimental drugs have been shown to delay disease progression in preclinical animal models of amyotrophic lateral sclerosis (ALS) but failed to show efficacy in human clinical trials or are still waiting for approval under Phase I-III trials. Riluzole, a glutamatergic neurotransmission inhibitor, is the only drug approved by the USA Food and Drug Administration for ALS treatment with modest benefits on survival. Recently, an antioxidant drug, edaravone, developed by Mitsubishi Tanabe Pharma was found to be effective in halting ALS progression during early stages. The newly approved drug edaravone is a force multiplier for ALS treatment. This short report provides an overview of the two drugs that have been approved for ALS treatment and highlights an update on the timeline of drug development, how clinical trials were done, the outcome of these trials, primary endpoint, mechanism of actions, dosing information, administration, side effects, and storage procedures. Moreover, we also discussed the pressing issues and challenges of ALS clinical trials and drug developments as well as future outlook.

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

Cited by 22 publications

References 27 publications

Disease-modifying effects of metabolic perturbations in ALS/FTLD

Disease-modifying effects of metabolic perturbations in ALS/FTLD

Current pathways for epidemiological research in amyotrophic lateral sclerosis

Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs

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