Multiple sclerosis New Drugs Review
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Daclizumab (Biogen, Abbott) Review: Multiple sclerosis - Krishan Maggon

Daclizumab (Biogen, Abbott) Review: Multiple sclerosis - Krishan Maggon | Multiple sclerosis New Drugs Review | Scoop.it
Daclizumab is a humanized monoclonal antibody which targets the CD25 alpha subunit of the high affinity receptor and inhibits...
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Can we find drugs that remove myelin debris more quickly | Multiple Sclerosis Society UK

Can we find drugs that remove myelin debris more quickly | Multiple Sclerosis Society UK | Multiple sclerosis New Drugs Review | Scoop.it
In MS, the immune system damages the protective myelin coating around nerve cells. In order for the brain to repair the damage with new myelin, it first has to get rid of the old myelin debris....
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Reactive astrocytes in multiple sclerosis impair neuronal outgrowth through TRPM7‐mediated chondroitin sulfate proteoglycan production - Kamermans - - Glia - Wiley Online Library

Reactive astrocytes in multiple sclerosis impair neuronal outgrowth through TRPM7‐mediated chondroitin sulfate proteoglycan production - Kamermans - - Glia - Wiley Online Library | Multiple sclerosis New Drugs Review | Scoop.it
Abstract

 

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS), characterized by inflammation‐mediated demyelination, axonal injury and neurodegeneration. The mechanisms underlying impaired neuronal function are not fully understood, but evidence is accumulating that the presence of the gliotic scar produced by reactive astrocytes play a critical role in these detrimental processes. Here, we identified astrocytic Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7), a Ca2+‐permeable nonselective cation channel, as a novel player in the formation of a gliotic scar. TRPM7 was found to be highly expressed in reactive astrocytes within well‐characterized MS lesions and upregulated in primary astrocytes under chronic inflammatory conditions. TRPM7 overexpressing astrocytes impaired neuronal outgrowth in vitro by increasing the production of chondroitin sulfate proteoglycans, a key component of the gliotic scar. These findings indicate that astrocytic TRPM7 is a critical regulator of the formation of a gliotic scar and provide a novel mechanism by which reactive astrocytes affect neuronal outgrowth.

 

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Understanding the link between our genes and our immune system in MS | Multiple Sclerosis Society UK

Understanding the link between our genes and our immune system in MS | Multiple Sclerosis Society UK | Multiple sclerosis New Drugs Review | Scoop.it
Researchers have identified over 200 genes that are linked to the risk of developing MS. Recent studies suggest that it’s how these genes are expressed in key immune cells that’s important in MS....
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Classifying brain microglia: Which are good and which are bad?

Classifying brain microglia: Which are good and which are bad? | Multiple sclerosis New Drugs Review | Scoop.it
Microglia are known to be important to brain function. The immune cells have been found to protect the brain from injury and infection and are critical during brain development, helping circuits wire properly.
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Biomedicines | Multiple Sclerosis: A Global Concern with Multiple Challenges in an Era of Advanced Therapeutic Complex Molecules and Biological Medicines

Biomedicines | Multiple Sclerosis: A Global Concern with Multiple Challenges in an Era of Advanced Therapeutic Complex Molecules and Biological Medicines | Multiple sclerosis New Drugs Review | Scoop.it
Multiple sclerosis (MS) has become a common neurological disorder involving populations previously considered to be infrequently affected. Genetic dissemination from high- to low-risk groups is a determining influence interacting with environmental and epigenetic factors, mostly unidentified.
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Increased mean R2* in the deep gray matter of multiple sclerosis patients: Have we been measuring atrophy? - Hernández‐Torres - - Journal of Magnetic Resonance Imaging - Wiley Online Library

Background Magnetic resonance relaxometry studies in multiple sclerosis (MS) have suggested that iron accumulates within deep gray matter (DGM) structures early in the disease course. However, the commonly utilized mean R2* and magnetic susceptibility measures reflect regional iron concentration but not a structure's total iron content. Thus, tissue atrophy could impact mean R2* and magnetic susceptibility estimates. Purpose To demonstrate that both average iron concentration and total iron content need to be reported in order to distinguish between atrophy‐related and definite magnetic susceptibility changes. Study Type Observational. Population The study was performed on 30 healthy controls (HCs) and 39 people with definite MS. Field Strength/Sequence 3T Philips Achieva using an 8‐channel SENSE head coil. R2* data were acquired using a multiecho gradient echo sequence and diffusion tensor imaging data were acquired using an echo‐planar sequence. Assessment Total iron content in DGM structures was assessed by calculating the sum of all R2* values within a region (denoted as ) and compared to the mean R2* as a measure of iron concentration. Statistical Test Significant group differences were investigated in a linear regression model. All DGM structures were assessed individually and the significance threshold was adjusted using the Bonferroni‐Holm correction for multiple comparisons. Results There was an increased mean DGM R2* in MS patients compared to HCs (significant in the pallidus, P = 0.0051). In contrast, in patients was found to be lower in the thalamus and the caudate (P = 0.0011) compared to HCs, and similar between the two cohorts in the other DGM regions. Data Conclusion An increase in mean R2* may not necessarily reflect increased iron accumulation. We propose as an additional metric to account for the effects of tissue atrophy when assessing tissue content changes, such as iron deposition or loss. Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.
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The effect of natalizumab on disability score and relapse rate of multiple sclerosis patients: a prospective cohort study | Clinical and Translational Medicine | Full Text

The effect of natalizumab on disability score and relapse rate of multiple sclerosis patients: a prospective cohort study | Clinical and Translational Medicine | Full Text | Multiple sclerosis New Drugs Review | Scoop.it
Multiple sclerosis (MS) is a progressive immune-related disorder of the central nervous system leading to destruction of myelin sheaths. Natalizumab is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin which has been approved for treatment of relapsing forms of MS. This study aims at determining the effect of natalizumab on expanded disability status scale (EDSS) score and relapse rate of MS patients. Fifty MS patients participated in the present prospective cohort study. Twenty patients (Mean age ± SD: 33 ± 6.03) received natalizumab and 30 patients (Mean age ± SD: 36.83 ± 7.24) were under treatment with IFN-β (control group). Patients were followed-up during a 12-month period. EDSS score and clinical signs were assessed monthly. Significant decreases were detected in EDSS score in natalizumab treated patients compared with the controls in months 10, 11 and 12. EDSS score showed a significant decrease in 80% of natalizumab treated patients. Number of relapses was significantly lower in natalizumab treated patients compared with control group. Natalizumab is effective in improvement of disability and reduction of relapse rate in MS patients.
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Severe hypertriglyceridemia associated with teriflunomide in a patient with multiple sclerosis: A case report - Carlos R Camara-Lemarroy, Joaquín Castilló, Jaume Sastre-Garriga, Mar Tintore, Xavier...

Objective: To describe a case of severe hypertriglyceridemia in a patient receiving teriflunomide. Methods: This is a case study. Results: Our patient developed...
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Advising patients seeking stem cell interventions for multiple sclerosis

Advising patients seeking stem cell interventions for multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
Given the intuitive potential of stem cell therapy and limitations of current treatment options for progressive multiple sclerosis (MS), it is not surprising that patients consider undertaking significant clinical and financial risks to access stem cell transplantation.
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Global and Regional Trends of Multiple Sclerosis Disability-Adjusted Life Years Rates: A 25-Year Assessment - Abstract - Neuroepidemiology 2019, Vol. 52, No. 1-2 - Karger Publishers

Global and Regional Trends of Multiple Sclerosis Disability-Adjusted Life Years Rates: A 25-Year Assessment - Abstract - Neuroepidemiology 2019, Vol. 52, No. 1-2 - Karger Publishers | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
Background: Multiple sclerosis (MS) burden of disease has been described by reporting the disability-adjusted life years (DALY) index. So far, no study has assessed the trend of MS DALY rates over time. Method: Age-standardized MS DALY rates for both sexes were reported every 5 years from 1990 to 2015 in 195 countries in the Global Burden of Disease Database (GBD) database. To assess the MS DALY rates’ trends in each super region and throughout the world, we applied the Latent Growth Models. We also utilized the linear mixed model to evaluate the effect of development factor on MS DALY rates. Results: Our results showed that 5 out of 7 GBD super regions had negative trends in MS DALY rates during these years and the remaining 2 – Latin America and the Caribbean (slope = 0.196, p < 0.05) and South Asia – slope = 0.057, p > 0.05 – had upward trends. Using a linear mixed model, we found that the mean difference of MS DALY rates was about 25 DALYs higher in developed countries compared to developing ones (p < 0.0001). Conclusion: In general, our findings revealed a global downward trend in the MS DALY rate. We also conclude that MS DALY rates are decreasing both in developed and developing countries, with a steeper slope in the developed world.
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Exogenous lipids in myelination and myelination. - PubMed - NCBI

Exogenous lipids in myelination and myelination. - PubMed - NCBI | Multiple sclerosis New Drugs Review | Scoop.it
Kaohsiung J Med Sci. 1997 Jan;13(1):19-29.Review...

 

Also human brain myelinogenesis can be affected by environmental factors. EFA deficiency has been well studied for the important role of C22:6 (a C18:3 metabolite) in the vision system development. The observation that dietary fatty acids can affect membrane composition has led to the use of modified diets in some CNS pathological conditions. For example, preterm infants characterized by low levels of C22:6 and fed with formulae diets enriched in this fatty acid, show a recovery of visual function. The administration of C22:6 has also been tested in patients affected by peroxisomal biogenesis disorders which are associated with very low levels of this fatty acid in the brain. During the treatment, C22:6 content increases in red blood cells, and probably in the brain membranes, as considerable neurologic and electrophysiological improvement suggest. A mixture of glyceryltrierucate and glyceryltrioleate has been tested in the demyelinating disease Adrenoleukodistrophy which is characterized by an abnormal accumulation of very long chain fatty acids (VLCFA) in tissues and fluids. The diet is able to lower VLCFA levels in plasma, but its efficacy for myelin damage is debated. Lastly, a diet which reduces the intake of saturated fatty acid and increases the quantity of polyunsaturates is suggested for multiple sclerosis patients since a decrease of linoleic acid in their plasma and erythrocytes has been observed. Such a diet seems able to reduce the severity of the attacks.

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UK Tiziana Life Sciences initiates Phase I trial with Foralumab

UK Tiziana Life Sciences initiates Phase I trial with Foralumab | Multiple sclerosis New Drugs Review | Scoop.it
Foralumab (TZLS-401)​
Foralumab (TZLS-401) has significant potential as the only fully human engineered anti-human CD3 antibody in clinical development with advantages of short duration of treatment regimen and reduced immunogenicity.

With Phase II development for Crohn’s Disease completed, modulation of T-cell response provides potential extension into a wide range of other autoimmune and inflammatory diseases, such as NASH, PBC, ulcerative colitis, multiple sclerosis and autoimmune Type-1 diabetes. Foralumab is being developed as both an immunosuppressive and immunomodulatory agent, with therapeutic benefits of rendering T-cells unable to orchestrate an immune response and induction of immune tolerance via maintenance of regulatory T-cells.
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Siponimod for the treatment of secondary progressive multiple sclerosis: Expert Opinion on Pharmacotherapy: Vol 0, No 0

Siponimod for the treatment of secondary progressive multiple sclerosis: Expert Opinion on Pharmacotherapy: Vol 0, No 0 | Multiple sclerosis New Drugs Review | Scoop.it
Siponimod may reduce the activity of the disease and has a modest effect on the gradual disability accrual. If approved, it may become one of the few available therapy options for secondary progressive MS.

KEYWORDS: BAF312, disease-modifying therapies, multiple sclerosis, progressive multiple sclerosis, siponimod, sphingosine 1-phosphate
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Magnetic resonance imaging in enterovirus‐71, myelin oligodendrocyte glycoprotein antibody, aquaporin‐4 antibody, and multiple sclerosis‐associated myelitis in children - Tantsis - - Developmental ...

Magnetic resonance imaging in enterovirus‐71, myelin oligodendrocyte glycoprotein antibody, aquaporin‐4 antibody, and multiple sclerosis‐associated myelitis in children - Tantsis - - Developmental ... | Multiple sclerosis New Drugs Review | Scoop.it
There are neuroimaging findings that are helpful in differentiating between myelitis associated with EV71, MOG, AQP4, and multiple sclerosis in children. These features may be useful early in the presentation of transverse myelitis while awaiting infectious/immunological testing, and/or further demyelinating events.

What this paper adds
Magnetic resonance imaging can help identify aetiologies for children presenting with a first episode of myelitis.
Entervirus‐71‐associated myelitis lesions are distributed throughout the cord and enhancement of nerve roots is common.
Lesions distributed throughout the cord are commonly seen in myelin oligodendrocyte‐associated myelitis.
Aquaporin‐4‐associated myelitis lesions are distributed in the cervicothoracic spine, cavitation and contrast enhancing lesions are common.
Short segment lesions in the cervicothoracic spine are commonly seen in multiple sclerosis‐associated myelitis.
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The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging Guan Y, Jakimovski D, Ramanathan M, Weinstock-Guttman B, Zivadinov R - Neural Regen Res

The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging Guan Y, Jakimovski D, Ramanathan M, Weinstock-Guttman B, Zivadinov R - Neural Regen Res | Multiple sclerosis New Drugs Review | Scoop.it
Neural Regen Res, Official publication of Publishing House of Neural Regeneration Research China Association of Rehabilitation Medicine,China...
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Relapse prevalence, symptoms, and health care engagement: patient insights from the Multiple Sclerosis in America 2017 survey

Relapse prevalence, symptoms, and health care engagement: patient insights from the Multiple Sclerosis in America 2017 survey | Multiple sclerosis New Drugs Review | Scoop.it
Relapses are a hallmark of multiple sclerosis (MS); the relapsing-remitting form,
RRMS, affects approximately 85% of the MS population [Berkovich, 2016; Goodin et al.,
2002, NMSS What is MS?, 2018]. While relapses are more common in patients with RRMS, all types of MS patients are subject to...
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A probiotic modulates the microbiome and immunity in multiple sclerosis - Tankou - 2018 - Annals of Neurology - Wiley Online Library

Objective Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing‐remitting multiple sclerosis (MS) patients. Methods MS patients (N = 9) and controls (N = 13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium, and Streptococcus twice‐daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2‐month treatment, and 3 months after discontinuation of therapy. Frozen peripheral blood mononuclear cells (PBMCs) were used for immune cell profiling. Stool samples were used for 16S rRNA profiling and metabolomics. Results Probiotic administration increased the abundance of several taxa known to be depleted in MS such as Lactobacillus. We found that probiotic use decreased the abundance of taxa previously associated with dysbiosis in MS, including Akkermansia and Blautia. Predictive metagenomic analysis revealed a decrease in the abundance of several KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways associated with altered gut microbiota function in MS patients, such as methane metabolism, following probiotic supplementation. At the immune level, probiotic administration induced an anti‐inflammatory peripheral immune response characterized by decreased frequency of inflammatory monocytes, decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes, as well as decreased human leukocyte antigen (HLA) D related MFI on dendritic cells. Probiotic administration was also associated with decreased expression of MS risk allele HLA‐DQA1 in controls. Probiotic‐induced increase in abundance of Lactobacillus and Bifidobacterium was associated with decreased expression of MS risk allele HLA.DPB1 in controls. Interpretation Our results suggest that probiotics could have a synergistic effect with current MS therapies. Ann Neurol 2018
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Are Cerebral Perfusion and Atrophy Linked in Multiple Sclerosis? Evidence for a Multifactorial Approach to Assess Neurodegeneration | BenthamScience

Are Cerebral Perfusion and Atrophy Linked in Multiple Sclerosis? Evidence for a Multifactorial Approach to Assess Neurodegeneration | BenthamScience | Multiple sclerosis New Drugs Review | Scoop.it
Background: Grey Matter (GM) atrophy has been extensively described in Multiple
Sclerosis (MS) patients, while cerebral hypoperfusion has been less consist...
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Safety and Efficacy of Fingolimod and Natalizumab in Multiple Sclerosis After the Failure of First-Line Therapy: Single Center Experience Based on the Treatment of Forty-Four Patients

Safety and Efficacy of Fingolimod and Natalizumab in Multiple Sclerosis After the Failure of First-Line Therapy: Single Center Experience Based on the Treatment of Forty-Four Patients | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
Background
In Poland, natalizumab or fingolimod treatment can be delivered as a second-line therapy to those patients with relapsing-remitting multiple sclerosis (RRMS) who demonstrated no response to interferon or glatiramer acetate treatment for a minimum of one year.

The objective of this study was to evaluate the impact of second-line therapy on the frequency of relapses, the disability progression, and the occurrence of side effects.

Material/Methods
Analysis covered 44 RRMS patients switched from first- to second-line therapy. The annualized relapse rate, disability progression (assessed with Expanded Disability Status Scale, EDSS) and MRI results (new or enlarged T2 lesions and new Gd-positive lesions) before and after switching were compared. The occurrence of adverse events was also assessed.

Results
The annualized relapse rate for second-line therapy was significantly lower than for first-line therapy (0.35±0.74 vs. 2.13±0.87, p=0.00005). Median of EDSS progression with first-line therapy was significantly higher than that with natalizumab or fingolimod treatment (p=0.00002).

The mean number of new or enlarged T2 and Gd+ lesions in MRI after one-year second-line treatment was significantly lower in comparison to lesions in MRI performed at the end of the first-line therapy (for T2: 0.61 vs. 4.56, p=0.0004; for Gd+: 0.13 vs. 1.98, p=0.0009). No significant differences in the clinical data, MRI results, and side effects between fingolimod and natalizumab patients have been observed.

Conclusions
Treatment with natalizumab or fingolimod as a second-line therapy in RRMS patients is safe and effective. Less restrictive criteria for switching should be considered.

MeSH Keywords: Drug Therapy, Combination; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
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Frontiers | Latitude, Vitamin D, Melatonin, and Gut Microbiota Act in Concert to Initiate Multiple Sclerosis: A New Mechanistic Pathway | Immunology

Frontiers | Latitude, Vitamin D, Melatonin, and Gut Microbiota Act in Concert to Initiate Multiple Sclerosis: A New Mechanistic Pathway | Immunology | Multiple sclerosis New Drugs Review | Scoop.it
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While the etiology of MS is still largely unknown, scientists believe that the interaction of several endogenous and exogenous factors may be involved in this disease. Epidemiologists have seen an increased prevalence of MS in countries at high latitudes, where the sunlight is limited and where the populations have vitamin D deficiency and high melatonin levels. Although the functions and synthesis of vitamin D and melatonin are contrary to each other, both are involved in the immune system. While melatonin synthesis is affected by light, vitamin D deficiency may be involved in melatonin secretion. On the other hand, vitamin D deficiency reduces intestinal calcium absorption leading to gut stasis and subsequently increasing gut permeability. The latter allows gut microbiota to transfer more endotoxins such as lipopolysaccharides (LPS) into the blood. LPS stimulates the production of inflammatory cytokines within the CNS, especially the pineal gland. This review summarizes the current findings on the correlation between latitude, sunlight and vitamin D, and details their effects on intestinal calcium absorption, gut microbiota and neuroinflammatory mediators in MS. We also propose a new mechanistic pathway for the initiation of MS.
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Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients – Newsemia

Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients – Newsemia | Multiple sclerosis New Drugs Review | Scoop.it
Latest Medical News & Articles...
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Aspirin ameliorates experimental autoimmune encephalomyelitis through interleukin-11–mediated protection of regulatory T cells

Aspirin ameliorates experimental autoimmune encephalomyelitis through interleukin-11–mediated protection of regulatory T cells | Multiple sclerosis New Drugs Review | Scoop.it
Aspirin is a common pain reliever that inactivates the enzyme cyclooxygenase, which is required for the synthesis of inflammatory prostaglandins and thromboxane. Mondal et al . found that aspirin also reduced the development of disease in mice with experimental autoimmune encephalitis (EAE), a model of multiple sclerosis (MS), by reversing the depletion of regulatory T cells (Tregs) that occurs during the disease. The effects of aspirin required the cytokine IL-11, which was itself sufficient to promote Treg stability and protect the mice from EAE development. These data suggest that low-dose aspirin regimens may benefit patients with MS.

Multiple sclerosis (MS) is a human disease that results from autoimmune T cells targeting myelin protein that is expressed within the central nervous system. In MS, the number of FoxP3-expressing regulatory T cells (Tregs) is reduced, which facilitates the activation of autoreactive T cells. Because aspirin (acetylsalicylic acid) is the most widely used nonsteroidal anti-inflammatory drug, we examined its immunomodulatory effect in mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We found that low-dose aspirin suppressed the clinical symptoms of EAE in mouse models of both relapsing-remitting and chronic disease. Aspirin reduced the development of EAE driven by myelin basic protein (MBP)–specific T cells and the associated perivascular cuffing, inflammation, and demyelination. The effects of aspirin required the presence of CD25+FoxP3+ Tregs. Aspirin increased the amounts of Foxp3 and interleukin-4 (IL-4) in T cells and suppressed the differentiation of naïve T cells into T helper 17 (TH17) and TH1 cells. Aspirin also increased the transcription of Il11 mediated by the transcription factor CREB, which was necessary for the generation of Tregs. Neutralization of IL-11 negated the effects of aspirin on Treg development and exacerbated EAE. Furthermore, we found that IL-11 alone was sufficient to maintain the percentage of FoxP3+ Tregs and protect mice from EAE. These results identify a previously uncharacterized mode of action of aspirin.
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Ocrelizumab may help preserve hand, arm function in PPMS

Ocrelizumab may help preserve hand, arm function in PPMS | Multiple sclerosis New Drugs Review | Scoop.it
(HealthDay)—For patients with primary progressive multiple sclerosis (PPMS), ocrelizumab reduces progression of upper-extremity (UE) impairment, according to an exploratory analysis published online Nov.
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Understanding treatment decisions from the perspective of people with relapsing remitting multiple Sclerosis: A critical interpretive synthesis

Understanding treatment decisions from the perspective of people with relapsing remitting multiple Sclerosis: A critical interpretive synthesis | Multiple sclerosis New Drugs Review | Scoop.it
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central
nervous system [Riñon et al., 2011, Köpke et al., 2004]. Around 85% of all people with MS are diagnosed with relapsing remitting MS RRMS [Milo and Miller, 2014, Barnett and Prineas, 2004] characterised by...
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Myelocortical Multiple Sclerosis: Neurodegeneration Without White Matter Demyelination –

Myelocortical Multiple Sclerosis: Neurodegeneration Without White Matter Demyelination – | Multiple sclerosis New Drugs Review | Scoop.it
The discovery of a new MS subtype using Cleveland Clinic’s rapid brain donation program suggests that the axon itself, rather than myelin, may be the primary site of injury in the disease.
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