Statins for multiple sclerosis

Sena, Armando; Pedrosa, Rui; Morais, M.G.

doi:10.1016/s0140-6736(04)16752-4

Cited by 8 publications

(6 citation statements)

References 4 publications

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“…Although statins may have some benefit for the disease activity of rheumatoid arthritis17 or multiple sclerosis,18 19 20 we found no evidence of a beneficial effect on SLE activity. Unlike most patients in whom liver enzyme elevation usually commences within the first 4 months of therapy,37 elevation of LFTs was common in this trial and occurred even late (18 months) in the trial.…”

Section: Discussioncontrasting

confidence: 62%

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Lupus Atherosclerosis Prevention Study (LAPS)

Petri

Kiani

Post

et al. 2010

Annals of the Rheumatic Diseases

201

123

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Section: Discussioncontrasting

confidence: 62%

“…In multiple sclerosis, treatment with atorvastatin reduced the number and volume of gadolinium-enhancing lesions in brain MRIs 18. Other studies with simvastatin and lovastatin have also shown beneficial effects of statins in multiple sclerosis 19 20…”

Section: Introductionmentioning

confidence: 99%

Lupus Atherosclerosis Prevention Study (LAPS)

Petri

Kiani

Post

et al. 2010

Annals of the Rheumatic Diseases

201

123

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“…This hypothesis is supported by data suggesting that MS patients who produce anti-IFNbeta binding antibodies have an increased incidence of autoreactive antibodies, including antiphospholipid and antithyroid antibodies [20]. The possible involvement of lipoprotein metabolism in NAbs production is of further interest in the context of other studies [7,8], implicating a disturbance of this metabolism in MS and the potential benefit of statin monotherapy in these patients [21].…”

Section: Discussionmentioning

confidence: 82%

Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

et al. 2010

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Interferon-beta (IFN-beta) therapy for multiple sclerosis (MS) is associated with a potential for induction of neutralizing antibodies (NAbs). Because immune reactivity depends on changes in lipoprotein metabolism, we investigated whether plasma lipoprotein profiles could be associated with the development of NAbs. Thirty-one female MS patients treated with subcutaneously administered IFN-beta were included. Demographic and clinical characteristics were compared between NAbs response groups using t tests for continuous and logistic regression analysis and Fisher's exact tests for categorical data, respectively. Multivariate logistic regression was used to evaluate the effect of potential confounders. Patients who developed NAbs had lower apoE levels before treatment, 67 (47-74) mg/L median (interquartile range), and at the moment of NAb analysis, 53 (50-84) mg/L, in comparison to those who remained NAb-negative, 83 (68-107) mg/L, P = 0.03, and 76 (66-87) mg/L, P = 0.04, respectively. When adjusting for age and smoking for a onestandard deviation decrease in apoE levels, a 5.6-fold increase in the odds of becoming NAb-positive was detected: odds ratios (OR) 0.18 (95% CI 0.04-0.77), P = 0.04. When adjusting for apoE, smoking habit became associated with NAb induction: OR 5.6 (95% CI 1.3-87), P = 0.03. These results suggest that apoE-containing lipoprotein metabolism and, possibly, tobacco smoking may be associated with risk of NAb production in female MS patients treated with IFN-beta.

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“…Likewise, Sena et al have shown in an earlier study that lovastatin treatment of MS patients reduces the number of T1 lesions in a number of patients, whereas disability scores remain stable and the majority of patients develop new T2-weighted lesions [103]. Although follow-up in this study lasted for 2 years [101], patient number was very low (n=7). In conclusion, more detailed knowledge on the actions of statins in the brain and larger, long-term, placebo-controlled clinical studies are needed before statins can truly be considered as save treatment options for MS.…”

Section: Treatment Potential Of Statins For Neurodegenerative Diseasementioning

confidence: 52%

“…These anti-inflammatory properties of statins would potentially be beneficial for the treatment of patients with autoimmune disorders. Therefore, statins are currently considered as possible treatment agents for MS and other neurodegenerative diseases [97][98][99][100][101][102][103]. Activation of microglia, the resident macrophages of the central nervous system, is thought to be a key element in the development of MS [104][105][106].…”

Section: Treatment Potential Of Statins For Neurodegenerative Diseasementioning

confidence: 99%

Putative Immune Regulatory Role of Statins

Kuipers¹,

Elsen

2006

CIR

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Statins, which are mainly used for treatment of hypercholesterolemia because of their lipid-lowering effects, may also display many immunomodulatory properties. Statins interfere in the mevalonate pathway through inhibition of HMG-CoA reductase activity and thereby affect isoprenylation of proteins and cholesterol biosynthesis. Besides lowering blood cholesterol levels, statins inhibit the production of pro-inflammatory cytokines and reduce membrane expression of several immunoregulatory molecules, including major histocompatibility complex class II (MHC-II) molecules. In this review we discuss the putative immunomodulatory role of statins and the mechanism by which simvastatin reduces the membrane expression of MHC-II molecules on several cell types, emphasizing on the disruption of cholesterol-containing microdomains, or lipid rafts, which transport and concentrate MHC-II molecules to the cell surface. Because glycosylphosphatidylinositol (GPI)-linked proteins are in general characteristic components of biochemically defined lipid rafts, and rely for transport and function at the cell surface on the integrity of these cholesterol-containing vesicles, we argue that statins, by disrupting these vesicles, also affect the expression of other immunoregulatory molecules. In addition, we also argue that statins inhibit the activation and intracellular transport of various proteins by interfering in protein isoprenylation. The interference in these processes results in reduced expression and function of membrane-bound molecules, which play important roles in the initiation and effector function of the immune response. Finally, we discuss the potential role of statins in the treatment of neuroinflammatory diseases.

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Statins for multiple sclerosis

Cited by 8 publications

References 4 publications

Lupus Atherosclerosis Prevention Study (LAPS)

Lupus Atherosclerosis Prevention Study (LAPS)

Influence of apolipoprotein E plasma levels and tobacco smoking on the induction of neutralising antibodies to interferon-beta

Putative Immune Regulatory Role of Statins

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