Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

Ratzer, Rikke; Börnsen, Lars; Dyrby, Tim B.; Christensen, Jeppe Romme; Ammitzbøll, Cecilie; Madsen, Camilla Gøbel; Garde, Ellen; Lyksborg, Mark; Andersen, Birgit; Hyldstrup, Lars; Sørensen, Per Soelberg; Siebner, Hartwig R.; Sellebjerg, Finn

doi:10.1177/1352458515605908

Cited by 23 publications

(28 citation statements)

References 18 publications

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“…Further, 60 weeks of monthly methylprednisolone therapy of 30 PMS patients did not influence the CSF OPN level either, although clinical and MRI measures improved (54). In contrast, 60 weeks of natalizumab treatment of 17 PMS patients reduced OPN significantly (47).…”

Section: Osteopontinmentioning

confidence: 80%

The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

Lycke

Zetterberg

2017

Expert Review of Clinical Immunology

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Multiple sclerosis (MS) is an immune-mediated chronic neurodegenerative disease of the central nervous system (CNS). Therapeutic interventions with immunomodulatory agents reduce disease activity and disability development, which are monitored clinically and by magnetic resonance imaging (MRI). However, these measures largely lack information on the impact from these therapies on inflammation, demyelination and axonal injury, the essential pathophysiological features of MS. Several biomarkers for inflammation and neurodegeneration have been detected in cerebrospinal fluid (CSF). In MS, some of these biomarkers seem to reflect disease activity, disability progression, and therapeutic response. Areas covered: In this review, we describe the most promising CSF biomarkers of inflammation and degeneration for monitoring therapeutic interventions in MS. We also describe the evolution of highly sensitive immunoassays that enable determination of neuron-specific biomarkers in blood. Expert commentary: Together with clinical and MRI measures, CSF biomarkers may improve the assessment of therapeutic efficacy and make personalized treatment possible. One disadvantage has been the need of repetitive lumbar punctures to obtain CSF. However, the technical development of highly sensitive immunoassays allows determination of extremely low quantities of neuron-specific proteins in blood. This will potentially open a new era for monitoring disease activity and treatment response in MS.

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Section: Osteopontinmentioning

confidence: 80%

The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

Lycke

Zetterberg

2017

Expert Review of Clinical Immunology

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“…EAE is a model of multiple sclerosis, a disease characterized by immune-mediated demyelination of the central nervous system, frequently resulting in disability (57). Intravenous or oral glucocorticoid treatment is commonly used in combination with other drugs for treatment of acute episodes and progressive disease (58,59). The EAE model is characterized by T-cell infiltration into the central nervous system causing inflammation and myelin damage (60).…”

Section: Cytokine Release By Monocytes Different Profiles Of Mifmentioning

confidence: 99%

Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential

Bloom

Metz

Nalawade

et al. 2016

Journal of Biological Chemistry

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Edited by Dennis VoelkerMacrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in a broad range of inflammatory and oncologic diseases. MIF is unique among cytokines in terms of its release profile and inflammatory role, notably as an endogenous counter-regulator of the anti-inflammatory effects of glucocorticoids. In addition, it exhibits a catalytic tautomerase activity amenable to the design of high affinity small molecule inhibitors. Although several classes of these compounds have been identified, biologic characterization of these molecules remains a topic of active investigation. In this study, we used in vitro LPS-driven assays to characterize representative molecules from several classes of MIF inhibitors. We determined that MIF inhibitors exhibit distinct profiles of anti-inflammatory activity, especially with regard to TNF␣. We further investigated a molecule with relatively low anti-inflammatory activity, compound T-614 (also known as the anti-rheumatic drug iguratimod), and found that, in addition to exhibiting selective MIF inhibition in vitro and in vivo, iguratimod also has additive effects with glucocorticoids. Furthermore, we found that iguratimod synergizes with glucocorticoids in attenuating experimental autoimmune encephalitis, a model of multiple sclerosis. Our work identifies iguratimod as a valuable new candidate for drug repurposing to MIF-relevant diseases, including multiple sclerosis.

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“…These controls with ONDs displayed no clinical and neuroradiologic features of MS and no signs of intrathecal inflammation as shown by the presence of oligoclonal bands, increased immunoglobulin G index, or pleocytosis (higher than upper normal limit, i.e., >5,000 cells/mL). The ethics committee of the Capital Region of Denmark approved the 2 intervention studies with natalizumab 10 (n = 24) and methylprednisolone 11 (n = 30). Written informed consent was obtained from all participants.…”

Section: Methodsmentioning

confidence: 99%

Absence of systemic oxidative stress and increased CSF prostaglandin F _2α in progressive MS

Lam

Maghzal

Khademi

et al. 2016

Neurol Neuroimmunol Neuroinflamm

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Objective:We aimed to investigate the role of oxidative stress in the progression of multiple sclerosis (MS).Methods:We determined by liquid chromatography–tandem mass spectrometry nonenzymatic (F2-isoprostanes) and enzymatic oxidation products of arachidonic acid (prostaglandin F2α [PGF2α]) in plasma and CSF of 45 controls (other neurologic disease [OND] with no signs of inflammation) and 62 patients with MS. Oxidation products were correlated with disease severity and validated biomarkers of inflammation (chemokine ligand 13; matrix metalloproteinase-9; osteopontin) and axonal damage (neurofilament light protein).Results:Compared with OND controls, plasma concentrations of F2-isoprostanes and PGF2α were significantly lower in patients with progressive disease, and decreased with increasing disability score (Expanded Disability Status Scale). In contrast, CSF concentrations of PGF2α, but not F2-isoprostanes, were significantly higher in patients with progressive disease than OND controls (p < 0.01). The content of PGF2α in CSF increased with disease severity (p = 0.044) and patient age (p = 0.022), although this increase could not be explained by age. CSF PGF2α decreased with natalizumab and methylprednisolone treatment and was unaffected by the use of nonsteroidal anti-inflammatory drug in secondary progressive MS. CSF PGF2α did not associate with validated CSF markers of inflammation and axonal damage that themselves did not associate with the Expanded Disability Status Scale.Conclusions:Our data suggest that MS progression is associated with low systemic oxidative activity. This may contribute to immune dysregulation with CNS inflammation accompanied by increased local cyclooxygenase-dependent lipid oxidation.

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Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

Abstract: Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS.

Cited by 23 publications

References 18 publications

The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential

Absence of systemic oxidative stress and increased CSF prostaglandin F _2α in progressive MS

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Monthly oral methylprednisolone pulse treatment in progressive multiple sclerosis

Abstract: Monthly methylprednisolone pulse treatment was safe, but had no effect on the primary outcome. However, improvements in secondary clinical and MRI outcome measures suggest that this treatment regimen may have a beneficial effect in progressive MS.

Cited by 23 publications

References 18 publications

The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

The role of blood and CSF biomarkers in the evaluation of new treatments against multiple sclerosis

Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential

Absence of systemic oxidative stress and increased CSF prostaglandin F 2α in progressive MS

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Absence of systemic oxidative stress and increased CSF prostaglandin F _2α in progressive MS