research

People with multiple sclerosis may be twice as likely to develop deep-vein blood clots, a condition known as venous thromboembolism, than healthy people do, a study reports. But data linking the two is limited, and its researchers say further work is needed to understand if MS is directly related to…

MS Patients Sought to Test Alternative Chronic Pain Treatment Methods Do you have serious pain issues along with your MS? If so, you might be interested in this study that’s looking for participants. By the way, who says that pain isn’t an MS symptom? A clinical trial…

Reducing body temperature during physical exercise can help rewire the brain and improve motor control in patients with multiple sclerosis (MS), a new research study at Canada’s Memorial University shows. Physical exercise can have several benefits for patients with MS, including improved strength and reduced symptoms of fatigue and…

Editor’s note: “Need to Know” is a series inspired by common forum questions and comments from readers. Have a comment or question about MS? Visit our forum. This week’s question is inspired by the forum topic “Have you tried the high dose biotin protocol?“, from…

Anxiety and depression are associated with lower cognitive abilities in patients with multiple sclerosis (MS) other and immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD) and rheumatoid arthritis, a study shows. These findings indicate the importance of managing symptoms of anxiety and depression in MS, as…

Stem cells tweaked in the laboratory have allowed researchers, reportedly for a first time, to generate and maintain ball-shaped cultures — called spheroids — of human brain cells in 3D that contain oligodendrocytes, the cells that produce myelin, along with neurons and the astrocytes that are essential to nerve cell health.

The question of how quickly to start a disease-modifying therapy (DMT) after a multiple sclerosis (MS) diagnosis is one that I frequently see when I browse online. It goes hand in hand with questions about which DMT is best to start with. There are many things to consider when…

Australian researchers from the University of Newcastle and the Hunter Medical Research Institute (HMRI) have received funding for two projects that will study unexplored areas in multiple sclerosis (MS). The projects, investigating the role of epigenetic differences in MS severity and treatment against MS-derived fatigue, received $211,000 AUD (about $151,300…

Herbicide Called Linuron Seen to Trigger Inflammatory Signals Linked to MS in Study This is only a mouse study, but this herbicide has been banned in Europe because of health concerns. Its effects seem worthy of further investigation. The herbicide linuron, commonly used with other herbicides, insecticides,…

The progressive decline in brain volume in multiple sclerosis (MS) patients, despite treatment with the disease-modifying therapy Tysabri (natalizumab), is driven by atrophy — shrinkage due to the degeneration of cells — in gray matter and not white matter structures, a new study reports. This finding points to new markers…

Subpopulations of oligodendrocytes — cells that produce the myelin sheath that protects nerve fibers — are altered in patients with multiple sclerosis, a study shows. These findings suggest that oligodendrocyte diversity and the different functions of these subpopulations might have a greater role in the disease than previously thought. The severity of MS varies greatly, and the patient's disability level does not correlate well with the degree of myelin loss. This suggests that other factors contribute to MS severity. One such factor may be that oligodendrocytes are heterogeneous — diverse in makeup and function. For example, oligodendrocytes in mouse spinal cords are known to naturally produce longer myelin sheaths than oligodendrocytes in the mouse brain. Additionally, individual oligodendrocytes have been shown to have different molecular makeups. However, the extent of human oligodendrocyte diversity and its possible contribution to MS pathology remains unknown. Researchers from the Karolinska Institutet and the MRC Centre for Regenerative Medicine studied the differences of individual human oligodendrocytes from healthy and MS brains to assess their diversity. Specifically, the team examined oligodendrocytes from the white matter areas of post-mortem human brains both from MS and non-MS patients. The team examined the RNA content — the messenger molecule carrying instructions from DNA for the production of proteins — from individual oligodendrocytes. Researchers identified groups of RNA molecules that defined features of oligodendrocytes from healthy human white matter. Some of these groups match those that defined oligodendrocytes in healthy mice. Strikingly, some of these RNA molecules in healthy brains were under-represented in oligodendrocytes from MS brains, whereas others were more prevalent. “We found that oligodendrocytes are a diverse population of cells and that different types are likely to have different functions in the brain,” Charles ffrench-Constant, the study's co-lead author, said in a Karolinska Institutet news release written by Katarina Sternudd. These differences in oligodendrocyte RNA content may indicate different functional states of oligodendrocytes in MS lesions. “The proportions of different resident oligodendrocytes in the lesions are changed, along with their properties, suggesting that they might have important roles in MS,” said Eneritz Agirre, PhD, a study co-author. Furthermore, the researchers believe that this altered diversity in oligodendrocytes in MS may be important to understand disease progression and develop therapeutic approaches. “Understanding which types of oligodendrocytes are most beneficial in repairing myelin will be crucial for maximizing the chances of developing much-needed treatments for MS,” said Anna Williams, PhD, study co-lead author. The team concluded that the changes in different oligodendrocyte subpopulations in MS suggest "a more complex role of these cells in the pathology of the disease, but also in regeneration of new cells,” said Gonçalo Castelo-Branco, PhD, another study co-lead author.

Tiny ruptures in the cell membrane of nerve fibers enable the entry of calcium and ultimately lead to their degeneration, a study in a mouse model of multiple sclerosis (MS) suggests. The study, “Calcium Influx through Plasma-Membrane Nanoruptures Drives Axon Degeneration in a Model of Multiple…

A protein marker for activated immune cells called Chi3I3 is key for the production of myelin-forming cells, and may become a target to boost myelin repair in multiple sclerosis (MS), according to a new study. The research, “Chi3l3 induces oligodendrogenesis in an experimental model of autoimmune…

Editor’s note: “Need to Know” is a series inspired by common forum questions and comments from readers. Have a comment or question about multiple sclerosis? Visit our forum. This week’s question is inspired by the forum topic “Can there be a connection between Epstein-Barr virus…

Endothelial cells, those lining the inside of small blood vessels, promote clearance of myelin debris — a common detrimental outcome of demyelinating diseases such as multiple sclerosis (MS) or spinal cord injury. However, in its path to clear the brain from myelin debris, endothelial cells trigger more damaging mechanisms, promoting…

Novartis and the University of Oxford’s Big Data Institute (BDI) have established an alliance to advance the use of medical data for spotting disease patterns and assessing patients’ responses to treatment. The initiative seeks to enable more informed clinical decision-making and improve the development of treatments for complex diseases.

Treatment with Ocrevus (ocrelizumab) has superior or comparable effectiveness and a similar safety profile to other available disease-modifying treatments (DMTs) for treating relapsing multiple sclerosis (MS), according to a new review study. The research, “Systematic review and network meta-analysis comparing ocrelizumab with other treatments for…

The herbicide linuron, commonly used with other herbicides, insecticides and fungicides to control the growth of grass and weeds, may be an important environmental risk factor in the development of neurological diseases that include multiple sclerosis, researchers suggest. Used in the U.S. and other countries — but recently…

A small molecule called Sephin1 may be able to significantly delay harm to neurons in multiple sclerosis (MS) by protecting oligodendrocytes, limiting the autoimmune response, a mouse study reports. The study, “Sephin1, which prolongs the integrated stress response, is a promising therapeutic for multiple sclerosis,” was published in the journal Brain. MS is thought to be caused by immune-mediated inflammation that damages the myelin — an insulating sheath around nerve cells. For this reason, current MS disease-modifying treatments focus on immune-mediated inflammation. Although these treatments moderate disease relapses, their impact on disease progression is unclear. Previous studies have demonstrated that oligodendrocytes — cells that produce myelin — are critical in protecting against neuron demyelination and axon (nerve fiber) damage. As a result, researchers have been keen to develop alternative therapeutic approaches that protect oligodendrocytes, and ultimately limit disease progression.  A signaling pathway called integrated stress response that acts as a natural defense system to protect cells has been shown to reduce the inflammatory impact on oligodendrocytes. This response is triggered by phosphorylation (a chemical reaction) of a protein called eukaryotic initiation factor 2 alpha (eIF2α), and reduces the total production of proteins, instead promoting the synthesis of protective proteins in the cells. Conversely, the integrated stress response can be cut off by dephosphorylation of eIF2α. Sephin1 was shown to inhibit the dephosphorylation of eIF2α, prolonging the protective response. In this study, researchers at the University of Chicago proposed that Sephin1, by producing this response, could protect oligodendrocytes and slow the progress of the disease. The team tested their hypothesis in a mouse model called experimental autoimmune encephalomyelitis (EAE), which is similar to MS in humans. Results showed that treatment with Sephin1 did inhibit eIF2α dephosphorylation in EAE mice, triggering a protective response against inflammation. More importantly, myelin-producing oligodendrocytes were also protected, and disease onset was significantly delayed. This correlated with diminished oligodendrocyte loss, protected neuronal axons and myelin, and prolonged integrated stress response. In addition, Sephin1 decreased the levels of inflammatory immune T-cells, and the production of inflammatory signals within the central nervous system. "By protecting oligodendrocytes and diminishing demyelination, we also reduce the generation of myelin debris,"  Brian Popko, PhD, the study's senior author, said in a press release. "The decreased exposure to myelin fragments should also limit the auto-immune response." Popko is the Jack Miller professor of neurological disorders, and director of the Center for Peripheral Neuropathy at the University of Chicago. The effects of Sephin1 were also combined with interferon-beta treatment — an anti-inflammatory first-line MS therapy. Researchers found that the combination was more effective than the therapies given separately. "Encouragingly, adding Sephin1 to the established anti-inflammatory MS drug interferon beta provided additive benefits to the mouse MS model," said study co-author Yanan Chen, PhD, a postdoctoral fellow in the Popko laboratory. The team concluded that the results "suggest that a neuroprotective treatment based on the enhancement of the integrated stress response would likely have significant therapeutic value for multiple sclerosis patients." Treatment with Sephin1, they say, "could lead to a better clinical outcome in multiple sclerosis patients as a safe neuroprotective drug, perhaps when used in combination with immune-modulatory therapies." Sephin1 has been patented and licensed to InFlectis BioScience, a French biotech company.

Relapsing-remitting multiple sclerosis (RRMS) patients on Gilenya (fingolimod) have fewer relapses and stay on treatment longer than those taking Tecfidera (dimethyl fumarate) or Aubagio (teriflunomide), according to a new study. The research, “Comparison of fingolimod, dimethyl fumarate and teriflunomide for multiple sclerosis,” was published…

Katerina Akassoglou, PhD, a leading neurology researcher at the Gladstone Institutes at the University of California, San Francisco (UCSF), won the 2018 Barancik Prize for Innovation in Multiple Sclerosis Research. Akassoglou will receive the award and deliver the Prize lecture at the Americas Committee for Treatment…

Mindfulness protects against depression, anxiety, fatigue, and sleep problems in patients with multiple sclerosis (MS), improving their quality of life and overall well-being, a study finds. The study, “Longitudinal associations between mindfulness and well-being in people with multiple sclerosis,” was published in the International Journal…

Treatment with a single dose of Ocrevus (ocrelizumab) depleted a subset of immune T-cells within two weeks in patients with relapsing multiple sclerosis (MS) or primary progressive MS (PPMS), according to a study. The study, “Ocrelizumab Depletes CD20+ T Cells in Multiple Sclerosis Patients,” was published in the journal Cells. Autoreactive immune T-cells, which attack the body’s own tissues, have been regarded as the primary mediator of MS; however, this view has been challenged by the effectiveness of therapies targeting immune B-cells that contain the CD20 cell surface protein in reducing disease activity. One such therapy is Genentech’s Ocrevus, an anti-CD20 monoclonal antibody, which was first approved in the U.S. in 2017 for patients with relapsing MS or PPMS. Because CD20 is mainly expressed by B-cell precursors and mature B-cells, Ocrevus is often considered to selectively deplete CD20-containing B-cells. However, CD20 is also expressed by highly activated T-cells with the CD3 protein marker, characterized by the increased production of proinflammatory molecules, or cytokines. These T-cells are found in the blood, cerebrospinal fluid — the liquid surrounding the brain and spinal cord — and chronic brain lesions of MS patients, and show an elevated expression of the CD8 and CD45 markers. Off-label use of rituximab (marketed as Rituxan in the U.S. and MabThera in Europe), a lymphoma and rheumatoid arthritis treatment that also targets CD20, has been associated with the depletion of CD20-containing T-cells in MS patients. Therefore, targeting this T-cell subtype has been hypothesized as an additional mechanism for rituximab’s clinical effectiveness. However, scientists did not know whether Ocrevus, which is different from rituximab in terms of CD20 binding and cell toxicity, also depletes CD20-positive T-cells. To address this unknown, a team from Hannover Medical School in Germany analyzed blood samples of MS patients through a technique called multicolor flow cytometry prior to the first dose of Ocrevus and after two weeks, immediately before the second dose. They intended to evaluate the characteristics of the patients’ peripheral blood mononuclear cells, which include T-cells, B-cells, monocytes, and macrophages. A total of 21 patients (13 women) were included, with a median age of 43 years (range 22-65 years). Of the participants, 17 had the relapsing form of the disease for a median of 14.6 years, while four had PPMS for a median of 5.6 years. The analysis found T-cells containing CD20 and CD3 in all patients. These cells accounted for 2.4% of all CD45-expressing lymphocytes — white blood cells that include T- and B-cells — and for a significant proportion (18.4%) of all CD20 cells. Evaluation of the cells’ fluorescence intensity revealed that CD20 levels were significantly lower on T-cells than on B-cells also expressing this marker. Treatment with one dose of Ocrevus substantially lowered the levels of CD20-positive T- and B-cells within two weeks, reflected by a frequency of 0.04% and an absolute cell count decrease from 224.9 to 0.57/microliter. “Our results demonstrate that treatment with [Ocrevus] does not exclusively target B-cells, but also CD20+ T-cells, which account for a substantial amount of CD20-expressing cells,” the researchers wrote. “These findings suggest that CD20+ T-cells might play a pivotal role in the pathogenesis of MS, and we speculate that depletion of CD3+CD20+ cells by anti-CD20 monoclonal antibodies might contribute to the efficacy of anti-CD20 therapy,” they added. However, they also emphasized that the findings need to be confirmed in studies with larger groups of MS patients.

Treating a common animal model of multiple sclerosis (MS) with a typhoid vaccine eased disease symptoms by prompting T helper cells to stop production of a pro-inflammatory factor — interleukin (IL)-17 — and by promoting greater numbers of anti-inflammatory  regulatory T-cells, researchers report. Their study, “Targeting prohibitins at the…

Exercise and multiple sclerosis are a natural pair and shown by research to be an important part of our MS care plan. We all can benefit from getting an assessment by a professional therapist and having an exercise plan customized for our MS, but accessing exercise in a…

A type of immune cell from the gut can reduce brain inflammation in people with multiple sclerosis (MS), and increasing the numbers of these cells in a mouse model of the disease halts inflammation completely, new research reports. These findings were reported in the study, “Recirculating…

Blood infection with the yeast Candida albicans, a type of fungus, can reach the brain and trigger an immune response, a new mouse study shows. Although the fungus can be cleared within 10 days, it affects the spatial memory of mice. These findings are the first evidence that a blood infection with a…

BrainStorm Cell Therapeutics announced that the production of its therapy NurOwn will be expanded to support upcoming clinical trials, namely a Phase 3 trial in amyotrophic lateral sclerosis (ALS) and a Phase 2 trial in progressive multiple sclerosis (MS). BrainStorm’s proprietary, stem cell-based technology called…

Biogen and Skyhawk Therapeutics have created a strategic partnership that will allow both companies to use Skyhawk’s SkySTAR technology platform for the discovery of new small molecule treatments for neurological diseases, including multiple sclerosis and spinal muscular atrophy. Under the terms of the agreement, Biogen will be given…

Immune cells in the intestine may reduce neuroimflammation in multiple sclerosis (MS) patients, a pre-clinical study suggests. Moreover, the augmented number of these cells was sufficient to suppress brain inflammation in an MS mouse model. The findings were reported in the study “Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via…