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Healthy Diet May Lower Risk of Developing MS, Study Finds

People who eat a healthy diet that includes foods such as vegetables, fish, eggs, poultry, and legumes may have a reduced risk of multiple sclerosis (MS), a study suggests. The study, “A healthy dietary pattern associates with a lower risk of a first clinical diagnosis of central nervous system…

Lemtrada Can Lower Number of B-cells Infiltrating Nervous System and Forming Clumps, Animal Study Shows

Treating mice in a model of multiple sclerosis with Lemtrada (alemtuzumab) prevented the formation of B-cell aggregates in the animals’ central nervous system and disrupted already existing ones, researchers report. The treatment also reduced disease activity when administered at the peak of disease. The study, “Anti-CD52 antibody treatment depletes B…

Quanterix’s Simoa Assay May Make Neurofilament Light Chain Useful Blood Biomarker of MS and Its Likely Progression

Quanterix’s ultra-sensitive Simoa assay has the potential to open new uses for the brain biomarker known as neurofilament light chain, including the possibility to detect early evidence of neurological diseases like multiple sclerosis (MS), Parkinson’s, and Alzheimer’s, and ably evaluate efforts to treat and prevent them, the company…

Smoking Increases Relapse Rate in RRMS Patients on Tysabri, Study Suggests

Smoking increases the relapse rate in patients with relapsing-remitting multiple sclerosis being treated with Tysabri , an observational study suggests. Multiple sclerosis is a multifactorial disease associated with both genetic and environmental risk factors. Smoking, in particular, has been linked to numerous aspects of MS, including its development and progression. In a previous study, the research team looked at how smoking influences the relapse rate in RRMS patients being treated with interferon beta. From more than 800 patients, they found that smoking one pack per day (about 20 cigarettes) essentially interfered with the positive effect of the IFN-beta treatment and increased the relapse rate by 27%. The researchers then questioned whether the same was true for other treatments. Tysabri, developed by Biogen, is a monoclonal antibody that targets the alpha-4 integrin protein. By interfering with this molecule, the therapy prevents white blood cells from moving into the central nervous system, suppressing the immune reaction that contributes to MS symptoms. In the study, 355 Tysabri-treated RRMS patients from the Danish Multiple Sclerosis Centre were assessed. To gather information on smoking habits and body mass index, the patients filled out a 100-question survey. Data was collected between the start of the treatment and a two-year follow-up visit. Results showed that smoking one pack of cigarettes per day increases the relapse rate by 38% in RRMS patients on Tysabri. This increase in relapse rate takes into account both sex and age at the start of treatment, since age can affect the relapse rate. For example, an increase in age by one year raises the number of relapses by 2%. The researchers also looked at the relationship between smoking and the presence of two immune-related alleles: HLA-DRB1*15:01 and HLA-A*02:01. Previous studies showed that HLADRB1*15:01 is associated with an increased risk of developing MS, while HLA-A*02:01 is linked to a decreased risk. Although previous studies reported a link between smoking and these two alleles in MS patients, the current study did not find an association between smoking and carrying either of these alleles. Based on the results, the researchers concluded that smoking significantly increases the relapse rate in RRMS patients receiving Tysabri. According to the team, the results "add important information that hopefully will sharpen the focus on the overall harmful effects of smoking in MS patients."

Vitamin D3 Insufficiency Increases MS Susceptibility in a Gene and Sex-dependent Manner

Vitamin D3 insufficiency increases multiple sclerosis (MS) susceptibility in a gene and sex-dependent manner, a mouse study suggests. The study with that finding, “Sex-Specific Gene-by-Vitamin D Interactions Regulate Susceptibility to Central Nervous System Autoimmunity,” by researchers at the University of Vermont, was published in the journal Frontiers in…

Blood Levels of IgG3 Antibodies May Predict Faster Shift to MS in Clinically Isolated Syndrome Patients, Study Says

Higher-than-usual levels of specific antibodies in the blood of patients with clinically isolated syndrome (CIS) may predict a faster progression to multiple sclerosis (MS), an Australian study reports. The specific antibody is known as IgG3, an immunoglobulin known to promote inflammation. The study, “Higher Serum Immunoglobulin G3 Levels May Predict…

Pregnancy Worsens Symptoms in MS Patients, Study Finds

Pregnancy, including successful delivery or miscarriage, worsens symptoms of multiple sclerosis (MS), as well as onset of the disease, a retrospective study shows. Researchers found the same effect of pregnancy on neuromyelitis optica spectrum disorders (NMOSD), an inflammatory disorder of the central nervous system characterized by demyelination and damage of…

Researchers Succeed at Generating Oligodendrocytes, Key to Myelin Renewal, in Tissue Created in Lab

Researchers at Case Western Reserve University School of Medicine have developed a cutting-edge laboratory technique able to turn human stem cells – special cells able to grow into any type of cell in the body – into brain-like tissues in a culture dish. They intend to use their tool to study how myelination – the deposition of myelin around nerve cells – occurs in the central nervous system, and how diseases such as multiple sclerosis (MS) impair this process. The experimental protocol to grow these structures outside an organis) is described in the study, "Induction of myelinating oligodendrocytes in human cortical spheroids," published in the journal Nature Methods. These structures, called “oligocortical spheroids,” are small spheres that contain all the major cell types usually found in the human brain, including oligodendrocytes — cells that produce myelin, which is the fatty substance that insulates nerve fibers. Previous cerebral organoid techniques failed to include oligodendrocytes. “We have taken the organoid system and added the third major cell type in the central nervous system — oligodendrocytes — and now have a more accurate representation of cellular interactions that occur during human brain development,” Paul Tesar, PhD, associate professor of genetics and genome sciences at Case Western's medical school and the study's senior author, said in a press release. Oligodendrocytes are essential to good brain health. Without these cells, myelin production is hampered and nerve cells cannot communicate effectively, and eventually they start to deteriorate. This is the starting point for many neurological disorders caused by myelin defects, including MS and rare pediatric genetic disorders like Gaucher disease. Using this new organoid system and these myelin-producing cells, researchers intend to study the process of myelination — how it occurs in normal circumstances and how neurodegenerative diseases disrupt this process. “This is a powerful platform to understand human development and neurological disease,” Tesar said. “Using stem cell technology we can generate nearly unlimited quantities of human brain-like tissue in the lab. Our method creates a ‘mini-cortex,’ containing neurons, astrocytes, and now oligodendrocytes producing myelin. This is a major step toward unlocking stages of human brain development that previously were inaccessible.” Researchers not only demonstrated that they were capable of generating mature oligodendrocytes derived from human stem cells in vitro, but they also showed these cells were able to exert their function and produce myelin starting at week 20 in a culture dish. Their improved organoid system could also be used to test the effectiveness of potential myelin-enhancing treatments. “These organoids provide a way to predict the safety and efficacy of new myelin therapeutics on human brain-like tissue in the laboratory prior to clinical testing in humans,” said Mayur Madhavan, PhD, co-first author on the study. To prove this point, researchers treated organoids with promyelinating compounds known to enhance myelin production in mice, and measured the rate and extent of oligodendrocyte generation and myelination. Under normal conditions, adding promyelinating drugs to cultured organoids increased the rate and extent of oligodendrocyte generation and myelin production, the team reported. But results differed in important ways using diseased organoids.  Specifically, treating organoids generated from patients with Pelizaeus-Merzbacher disease — a fatal genetic myelin disorder — brought an in vitro recapitulation of the patients' symptoms. “Pelizaeus-Merzbacher disease has been a complicated disorder to study due to the many different mutations that can cause it and the inaccessibility of patient brain tissue,” said Zachary Nevin, PhD, co-first author on the study. “But these new organoids allow us to directly study brain-like tissue from many patients simultaneously and test potential therapies.” Altogether, these findings demonstrate that oligocortical spheroids could be a versatile in vitro system to study how myelination occurs in the central nervous system, and a possible model for testing new therapies for neurodegenerative disorders. “Our method enables generation of human brain tissue in the laboratory from any patient,” Tesar said. “More broadly, it can accurately recapitulate how the human nervous system is built and identify what goes wrong in certain neurological conditions.”

African-Americans Show Better Adherence and Satisfaction with Gilenya Than Injectable DMTs, Phase 4 Study Finds

African-Americans with relapsing–remitting multiple sclerosis (RRMS) show higher adherence and greater satisfaction when treated with oral Gilenya (fingolimod, by Novartis) than with injectable therapies, according to a new study. The research, “Treatment retention on fingolimod compared with injectable multiple sclerosis therapies in African-American patients: A…

Cladribine Added to Interferon-beta Seen to Lower Relapses in Active MS, But Safety Questioned

Cladribine tablets added to interferon-beta treatment significantly reduced the probability of relapses over 96 weeks in people with active relapsing multiple sclerosis , a Phase 2 clinical trial found. But a troubling diminishment in key immune cells was also seen in treated patients. Relapsing-remitting MS is marked by periods of flares caused by inflammatory attacks, followed by periods of partial or complete recovery . A majority --about 65 percent -- go on to develop secondary progressive MS. Despite the growing number of treatment options — including disease-modifying therapies — for these MS patients, efforts continue into better ways to lower relapse frequency and slow disease progression. Researchers tested the safety and efficacy of cladribine tablets as an add-on therapy in patients continuing to experience active relapses while under interferon-beta treatment. Cladribine is an oral medication that works by selectively targeting and reducing the number of immune cells involved in the inflammatory attacks occurring in active MS. It was developed by EMD Serono (Merck KGaA outside the U.S. and Canada) and approved in the European Union using the brand name Mavenclad (it is not approved in the U.S. for MS). Interferon-beta works by balancing pro- and anti-inflammatory signals, reducing the number of immune cells and promoting the survival of nerve cells. Interferon-beta therapies are marketed under several brand names; in the study, researchers analyzed patients using Rebif (marketed by EMD Serono), Avonex (by Biogen), and Betaseron/Betaferon (by Bayer). The 96-week, randomized, double-blind, Phase 2b trial called ONWARD enrolled a total of 172 patients with active relapsing MS, who were randomly divided into two groups: those given cladribine tablets together with interferon-beta, and those that received a placebo and interferon-beta. Results showed those taking cladribine tablets together with interferon-beta had 63% lower likelihood of a relapse compared to those given an add-on placebo. Add-on cladribine treatment also reduced most measures of disease activity as assessed by magnetic resonance imaging (MRI) — namely, the number of new brain and spinal cord lesions. However, almost half of patients in this treatment group developed lymphopenia, a condition where the levels of lymphocytes (important immune white blood cells) in the blood are abnormally low. None in the control group developed the condition. Other reported side effects, including other serious adverse side effects, were identical in the two groups. Altogether, the findings indicate that a cladribine and interferon-beta combination can successfully lower the probability of relapses over the course of 96 weeks, but also increase a person's chances of lymphopenia.