research

Oligodendrocyte precursor cells (OPCs), the cells responsible for myelin production, are unable to migrate into sites of myelin loss in the brain. These cells then cluster and disrupt the blood-brain barrier (BBB), triggering an inflammatory process in the early stages of multiple sclerosis (MS), a study shows. The study, “Aberrant oligodendroglial–vascular interactions disrupt the blood–brain barrier, triggering CNS inflammation,” was published in the journal Nature Neuroscience. MS is an autoimmune disease characterized by the loss of myelin (demyelination) — the fat-rich substance that protects nerve fibers — which leads to neurodegeneration. Along with loss of myelin, researchers have observed that the blood-brain barrier — a highly selective membrane that shields the central nervous system with its cerebrospinal fluid from the general blood circulation — breaks down in the initial stages of disease. A team led by researchers at the University of California, San Francisco, have now discovered that OPCs are involved in the disruption of the blood-brain barrier in MS, according to a press release from the National MS Society, which funded the study. Oligodendrocytes are myelin-producing cells and are responsible for myelinating the nerve cells’ axons — a single oligodendrocyte is capable of myelinating multiple axons. Mature myelin-producing oligodendrocytes develop from more immature, stem cell-like OPCs. In a normal brain, upon myelin loss, OPCs are called into action and travel into the damage site where they mature and generate myelin-producing oligodendrocytes. In this study, the researchers found that OPCs in MS form clusters in blood vessels of the brain-blood barrier, having lost the ability to detach from these vessels and migrate to injury sites. In an animal model of MS, they saw that OPC aggregates altered the location of other cells — called astrocytes — in a competition for space, and contributed to the disruption of blood vessels. Astrocytes are a group of star-shaped cells, belonging to the group of glial cells, that provide neurons with energy, and work as a platform to clean up their waste. They also have other functions within the brain, such as regulating blood flow and inflammation. The team also observed that OPC aggregates trigger an immune inflammatory response, shown by a large number of microglia (the central nervous system immune cells) and immune cells called macrophages around these cell clusters. “We find in several MS cases, in lesion areas with active inflammation, that OPCs can be found clustered on vasculature, representing a defect in single cell perivascular migration and inability to detach from blood vessels,” the researchers wrote. Further molecular analysis revealed that OPCs have high levels of Wnt signaling, and elevated secretion of Wif1 factor to the extracellular space that could explain why OPCs accumulate and destroy the blood-brain barrier. The WiF1 factor is actually a negative regulator of Wnt signaling that is essential for the maintenance of the blood-brain barrier structure. This factor competes with Wnt ligands, and affects the integrity of cellular junctions, making the blood-brain barrier more fragile and permeable. "Evidence for this defective oligodendroglial–vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB,” the researchers wrote. They suggested that more studies are needed to better understand the interactions between blood vessels and oligodendrocytes, which could help identify new therapeutic targets for promoting myelin repair in MS.

The National Multiple Sclerosis Society has granted $24.4 million to fund 64 multiple sclerosis (MS) research projects and training fellowships worldwide. This is the latest funding initiative by the Society, which is planning to invest a total of $35 million in 2019 to support 340 MS studies ongoing across…

A collaboration between DNAnexus, the Sutter Health network, and the University Pittsburgh Medical Center (UPMC) aims to improve personalized medicine in multiple sclerosis (MS) through the first large-scale clinical genomic research study, the companies announced. The network has the goal of improving screening, diagnosis, and treatment of…

Progressive multifocal leukoencephalopathy, more commonly referred to as PML, is a brain infection that’s frequently fatal. PML is particularly dangerous to people with MS, which is why I’m interested in a report about a medication that’s showing promise as a PML treatment. The concern for people with MS is…

Cognitive and neuropsychiatric problems caused by relapsing-remitting multiple sclerosis (RRMS) — such as memory and processing issues, depression, and irritability — are the main source of strain among life partners of MS patients with mild disability, a study finds. The study, “Caregiver strain among life partners…

A new web portal called Talk2Me that detects early changes in language could help doctors diagnose or determine progression in neurodegenerative disorders like multiple sclerosis (MS), the scientists who created it suggest. The open platform portal, which gathers language data through an array of cognitive tasks performed…

This year’s John Dystel Prize for Multiple Sclerosis Research is being awarded to Anne H. Cross, a neurologist and MS chair in the department of neuroimmunology at  Washington University School of Medicine in St. Louis, for her research into the role of immune B-cells in multiple sclerosis attacks and new imaging…

A protein that promotes nervous system repair through remyelination — the creation of myelin, the protective sheath around nerve cells — in mice also is found in remyelinating plaques in brains of multiple sclerosis (MS) patients, new research shows. This protein potentially represents a new therapeutic target in demyelinating…

A link between fat molecules called ceramides and worsening disease in overweight and obese people with multiple sclerosis appears to exist, a study reports, with its findings suggesting that ceramides prompt the growth of immune cells called monocytes, which in turn spurs disease progression. These results also strengthen the likelihood that lifestyle factors, like diet and weight, can act as disease modifiers, its researchers said. High body mass index has been linked to the risk of developing MS, but for reasons that aren't clear. One idea is that weight-induced differences in lipids (fat molecules) in the blood, because they are involved in several cellular signaling processes, may affect MS and its course in people with higher BMIs. To test this hypothesis, a team led by researchers at the Advanced Science Research Center (ASRC) at The Graduate Center and at the Icahn School of Medicine at Mount Sinai analyzed 54 patients with relapsing-remitting MS (MS), ages 18 to 60, and with normal or high BMIs (27 people in each group). Participants were followed for two years. BMI is a measure of body fat based on height and weight. A normal BMI is defined as one between 18.5 and 24.9, while a person is considered overweight with a BMI of 25–29.9, and obese it is 30 or higher. Researchers took blood samples, and looked for differences between the groups in terms of both immune cells and blood lipid profiles. They then validated their findings in a separate group of 91 RRMS patients. Patients with high BMIs tended to have more monocytes than those with normal BMIs. Monocytes can travel through the blood to tissues where they develop into macrophages, immune cells with various functions that are best known for "eating" invading bacteria. Monocytes can also travel to the brain and damage nerve fibers. Overweight and obese patients also had significantly higher levels of ceramides compared with normal-weight patients, and the researchers wondered if a link might exist between the two. Through a set of experiments in cells, they discovered that ceramides cause epigenetic changes in monocytes; that is, they alter the way their genomes are "read," so they alter gene activity. Specifically, ceramide-treated cells showed a type of epigenetic change called methylation — which generally turns genes "off" — in genes that normally help prevent cells from dividing. Conceptually, these genetic changes serve to unleash monocytes, leading them to grow more (proliferate) than they otherwise might. The researchers also found more methylation on the genomes of monocytes from high-BMI patients than those from low-BMI patients, and they noted that the overweight or obese patients also tended to have greater disease activity, worse disability progression, and more brain lesions on MRI (magnetic resonance imaging) scans on follow-up. Finally, the researchers tested a mouse model of MS, giving one group of mice a standard diet and another a high-fat diet. Mice fed the high-fat diet were found to have greater disease severity, more brain lesions, and more monocytes, confirming the findings seen in MS patients. "This study gives us a much-needed view into the environmental influences that can affect and change the behavior of cells in an individual's body," Kamilah Castro, the study's first author, said in a press release. "Our findings suggest that increased levels of saturated fat as a result of dietary habits are one likely cause of the epigenetic changes that advance MS, which gives us a starting point for a potential intervention." According to the team, the findings support the concept of nutri-epigenomics: that is, the ability of food to alter the way the genetic information is interpreted by each cell, and suggest that "weight management and dietary intervention" might affect MS prognosis. One limitation was the study's small size, its researchers noted. "While we consider our results … very exciting and mechanistic, we acknowledge that the potential consideration of ceramide levels as biomarkers for disease progression in MS would require validation ... using larger cohorts with a longitudinal and/or cross-sectional design," they concluded. "It will also be important to evaluate the effectiveness of dietary intervention (with an emphasis on the reduction of specific classes of saturated fats), as potential modulator of plasma ceramide levels and possibly of disease course in MS patients."

Rituximab-treated multiple sclerosis (MS) patients who take vitamin D supplements have less inflammatory activity, a study reports. Increased levels of vitamin D were associated with beneficial treatment outcomes, such as better self-perceived health and reduced levels of the inflammation marker C-reactive protein…

Tecfidera (dimethyl fumarate) is more efficient at preventing relapses, and has a lower discontinuation rate than Aubagio (teriflunomide), according to a Danish study. The study “Comparative effectiveness of teriflunomide and dimethyl fumarate: A nationwide cohort study” was published in the journal Neurology. Aubagio (marketed by Sanofi Genzyme) and Tecfidera…

Nearly 18% of new multiple sclerosis (MS) patients referred to two speciality clinics in Los Angeles, California, had been misdiagnosed with the disease, according to a recent study. Most of them actually were affected by migraines, among other…

A woman’s age at her first menstruation, or becoming pregnant and breastfeeding does not substantially influence the long-term risk of multiple sclerosis (MS) or the risk of increased disability, a study of a large number of patients with clinically isolated syndrome…

Roche Canada is contributing $2.125 million to the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo), a partnership initiative with the Multiple Sclerosis Society of Canada, the Brain Canada Foundation, and Biogen Canada. The addition of Roche Canada to the collaboration raises the…

The amount of zinc, iron, and other minerals a person has in his or her diet is not associated with the risk of developing multiple sclerosis (MS), according to a study. The study, “Total intake of different minerals and the risk of multiple sclerosis,” was published…

High blood levels of a signaling protein known as TWEAK are associated with active neuroinflammation in patients with multiple sclerosis (MS), a study shows. This finding suggests that TWEAK may be a valuable biomarker to assess ongoing inflammation and overall MS activity, and potentially help optimize patient care. The…

A shortened DNA molecule showed an increased ability to bind myelin in human cells, and may boost the development of remyelination approaches for multiple sclerosis (MS) treatment, according to a study. The study, “Optimization of a 40-mer Antimyelin DNA Aptamer Identifies a 20-mer with Enhanced Properties…

In partnership with the Canadian Institutes of Health Research, the MS Society of Canada has announced $1.5 million to fund research over five years on the effects of cannabis on multiple sclerosis (MS) symptoms and disease progression. Studies have shown that for each 10-degree increase in latitude, patients newly diagnosed…

Texas Tech University Health Sciences Center (TTUHSC) El Paso has received a $750,000 gift to establish an endowed chair in the department of neurology. TTUHSC will match that donation to provide a total of $1.5 million that will be used to recruit and attract physicians in specialty areas that are underserved in…

T20K, Cyxone‘s lead compound for treating multiple sclerosis (MS), seems able to prevent or slow disease progression, according to data from preclinical studies. Based on these findings, the company is confident that T20K might become a prophylactic (preventive) medication for MS in the near future. T20K is a…

Body mass index (BMI), but not the age at which people start puberty, could increase the risk of multiple sclerosis (MS), a study suggests. The study, “Effect of age at puberty on risk of multiple sclerosis: A mendelian randomization study,” was published in the journal …

A Phase 3 trial testing ADS-5102 (amantadine) extended release capsules in all types of multiple sclerosis (MS) is enrolling participants to determine whether the oral therapy can improve walking speed. A total of 570 adults with MS, ages 18 to 70 years, who have difficulty walking will be…

Schwann cells surrounding neurons protect the degeneration of nerves by blocking thrombin, a blood-clotting protein that can also damage nerves, according to a new study. These findings may aid in the further understanding of genetic and molecular mechanisms behind conditions such as multiple sclerosis (MS). Results of the study, “Glial cells…

Non-contrast MRI Effective in Monitoring Progression of MS, Study Shows There’s been increased interest in the risks versus the benefits of using gadolinium to make lesions more visible on an MRI. The U.S. Food and Drug Administration issued an advisory last year raising the level of…

The first patient has been enrolled in a Phase 2 multicenter clinical trial testing the use of NurOwn cellular therapy to treat progressive multiple sclerosis (MS), BrainStorm Cell Therapeutics announced. The open-label trial (NCT03799718), titled Safety and Efficacy of Repeated Administration of neuron (MSC-NTF Cells) nin Participants…

The evaluation of disease progression in multiple sclerosis (MS) patients through magnetic resonance imaging (MRI) can be performed without the use of a contrast agent, new research has shown. These findings suggest that routine use of contrast-enhanced MRI is unnecessary for most follow-ups with MS patients, reducing both imaging…

Increased production of an anti-inflammatory molecule called interleukin (IL)-10, and suppression of a subtype of immune T-cells, may mean that a fatty acid called pentanoate is effective against inflammatory and autoimmune diseases such as multiple sclerosis (MS), according to new research in mice. The study, “The…

Women with multiple sclerosis (MS) do not experience more relapses right after giving birth, as previously believed, according to a preliminary study. The study also revealed that mothers with MS who breastfeed their babies have a lower relapse risk compared with those who do not breastfeed. The data, “…

Treating multiple sclerosis with Tecfidera induces specific genetic alterations that may reduce the levels of immune T-cells targeting the central nervous system, researchers report. Environmental stimuli may induce epigenetic changes in cells — meaning not alterations in the genes themselves, but changes in gene expression (the process by which information in a gene is synthesized to create a working product, like a protein). Epigenetic changes may induce MS development, as these alterations can cause T-cells to attack the central nervous system. One type of epigenetic change is DNA demethylation, the removal of methyl chemical groups, in which molecules involved in metabolism (such as fumarate) interact with enzymes known as DNA demethylases. This process in key for T-cell activation, function and memory, suggesting that it could be an immunomodulatory target. Fumaric acid esters were shown to be effective in MS clinical trials, leading to the approval of Tecfidera (by Biogen) for people with relapsing-remitting forms of the disease. However, their complete mechanism of action remains unclear. Aiming to address this gap, scientists at the Advanced Science Research Center (ASRC) at The Graduate Center of The City University of New York and the Icahn School of Medicine at Mount Sinai, recruited 98 MS patients, either previously untreated (47 people, mean age of 38.4), treated with Tecfidera (35 people, mean age of 42.3), or treated with glatiramer acetate (16 patients, mean age of 43.4) — marketed as Copaxone by Teva Pharmaceuticals, with generic forms by Sandoz (as Glatopa) and by Mylan. All patients had stable disease for at least three months, but disease duration was shortest in untreated patients — 40.4 months vs. 130 months in those given Tecfidera, and 100 months in patients using glatiramer acetate. Blood samples were collected from each participant to assess epigenetic changes in T-cells expressing the cell surface marker CD4. MS patients typically have an activated form of these cells in their blood and cerebrospinal fluid, the liquid surrounding the brain and spinal cord. Results revealed that, compared to the other two groups, treatment with Tecfidera was associated with a lower percentage of T-cells containing the CD3, CD4, and CD8 markers, as well as lower levels of subsets of T-cells expressing the CCR4 and CCR6 receptors, which are critical to T-cell migration to the gut, brain, and skin. Treatment with glatiramer acetate resulted in significantly milder alterations in T-cell percentages compared to no treatment. Researchers then found that FAEs induce excessive methylation — the addition of methyl groups — in T-cells containing CD4, compared to glatiramer acetate. Specifically, this overmethylation was observed in a micro-RNA — tiny RNA molecules than control gene expression — known as miR-21, key for the differentiation of a subset of T-cells called T helper-17 (Th17) cells and for CCR6 expression in MS mouse models. These Th17 cells are critical in tissue inflammation and destruction, and have been implicated in MS. The epigenetic effects of FAEs were subsequently validated by comparing pre- to post-treatment with Tecfidera in seven patients. In turn, in vitro (lab dish) experiments showed that FAEs act specifically on the activation of naïve T-cells — those able to respond to new pathogens to the immune system — containing the CD4 or the CD8 markers. Of note, patients with MS have shown increased miR-21 levels, particularly during acute relapses. As such, the team hypothesized that its hypermethylation by FAEs could contribute to remission and the prevention of relapses in this patient population. These results "suggest that the metabolic-epigenetic interplay in T-cells could be harnessed for therapeutic purposes," the researchers wrote, and that the immunomodulatory effect of FAEs in MS is due at least in part to the epigenetic regulation of T-cells. The researchers believe that their findings have a broader implication, beyond MS. "Our findings about therapeutically active metabolites have implications for the treatment of not only multiple sclerosis but also other autoimmune diseases, such as psoriasis and inflammatory bowel disease, which involve the same type of T-cells," Achilles Ntranos, the study’s lead author, said in a press release. "Understanding the epigenetic effect of metabolites on the immune system will help us develop several novel strategies for the treatment of autoimmune diseases, which could help patients and physicians achieve better clinical outcomes," Ntranos added. Patrizia Casaccia, the study’s senior author, concluded: "It may one day be possible to target and suppress production of the specific brain-homing T-cells that play a role in the development of MS."

A daily cup of flavonoid-rich cocoa may help ease fatigue in people with relapsing-remitting multiple sclerosis (RRMS), according to the results of a small clinical trial. The study “A randomised double-blind placebo-controlled feasibility trial of flavonoid-rich cocoa for fatigue in people with relapsing and remitting multiple sclerosis” was…