News

February 1, 2019 News by Alice Melão, MSc

Study Shows Benefits of Low Temperature Exercise for MS Patients

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…

January 29, 2019 News by Patricia Inacio, PhD

Gilenya Better at Lowering Relapse Rate than Tecfidera or Aubagio, Study Suggests

Gilenya is linked to significantly lower annualized relapse rates in relapsing-remitting multiple sclerosis (RRMS) patients compared to Tecfidera or Aubagio, a study suggests. All three therapies showed similar effects on disability outcomes. Oral immunotherapies — including Novartis’ Gilenya, Biogen’s Tecfidera, and Sanofi Genzyme’s Aubagio — are currently standard therapies for RRMS treatment. But while these therapies are highly effective at modulating MS activity, studies comparing their efficacy on relapse and disability are missing. This is an important point for MS patients, so that if a change in oral therapies is needed (due to lack of tolerance, for example), the decision on a more suitable therapy is based on scientific evidence. To address this matter, a group of researchers used the MsBase, an international observational MS cohort study, to identify RRMS patients who had been treated with Gilenya, Tecfidera, or Aubagio for at least three months. The team compared Tecfidera versus Aubagio, Gilenya versus Aubagio, and Gilenya versus Tecfidera, specifically for the therapy’s impact on relapse activity, six-month disability worsening or improvement, and persistence of treatment. Relapse was defined as the occurrence of new symptoms or exacerbation of existing ones for a period of over 24 hours, at least 30 days after a previous relapse. Disability was assessed using the Expanded Disability Status Scale (EDSS); the six-month disability worsening or improvement were defined as an increase or a decrease by one value in EDSS. The study included 614 patients treated with Aubagio, 782 with Tecfidera, and 2,332 with Gilenya. Patients were followed over a median of 2.5 years. Patients’ characteristics at baseline differed among the three groups. Aubagio-treated patients tended to be older, with longer periods of disease, fewer relapses, and lower EDSS scores compared to the other two groups. Patients treated with Gilenya had higher EDSS and more relapses during the prior year, compared to those treated with Tecfidera. The majority of the patients had been treated with other immunotherapies prior to being given one of these three oral treatments. Results showed that Gilenya-treated patients had significantly lower annualized relapse rates than those treated with Tecfidera (0.20 versus 0.26) or Aubagio (0.18 versus 0.24), while patients taking either Tecfidera or Aubagio had a similar rate. However, during the 2.5-year period analyzed, researchers found no differences in disability accumulation or disability improvement among the three therapies. Regarding treatment persistence, Tecfidera and Aubagio were more likely to be discontinued than Gilenya. Overall, the results suggest that treatment with Gilenya may have a greater impact on relapse frequency in RRMS patients compared to Tecfidera and Aubagio, although the "effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment," researchers said. “Choosing a therapy in individual patients remains a complex task that requires thorough and individualized evaluation of disease prognosis, and the corresponding risks and benefits of the increasing number of available therapies,” they concluded.

January 29, 2019 News by Santiago Gisler

Funding Supports MS Research on Epigenetics and Fatigue in Australia

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…

January 28, 2019 News by Jonathan Grinstein

Altered Oligodendrocyte Diversity Contributes to Multiple Sclerosis, Study Suggests

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.

January 24, 2019 News by Patricia Inacio, PhD

Study of Myelin Debris Sheds Light on Brain Inflammation in MS

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…

January 24, 2019 News by Jonathan Grinstein

New Products Intended to Stimulate Feet of MS Patients

Naboso Technology has expanded its product offerings with new insoles and training mats specifically designed to stimulate the nervous system through the skin on the bottom of the feet. The products were developed to help improve balance, posture, movement and restore motor function, as part of a neurorehabilitation strategy…

January 21, 2019 News by Jonathan Grinstein

Fatigue More Common in Progressive MS Patients, Survey Shows

Fatigue is more prevalent among patients with progressive multiple sclerosis (MS), according to a study that surveyed patients on fatigue and factors related to it. In addition, increased fatigue severity correlated with greater physical, cognitive, and psychological impairment, although the strength of this link was largely the same…

January 18, 2019 News by Jonathan Grinstein

Small Molecule Shows Ability to Limit Autoimmune Response in MS, Mouse Study Reports

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.

January 18, 2019 News by Patricia Inacio, PhD

Blood Stem Cell Transplant Better than DMTs at Reducing Risk of Disease Progression in RRMS

Autologous hematopoietic stem cell transplant is better than disease-modifying therapies (DMT) at reducing the risk of disease progression in patients with relapsing-remitting multiple sclerosis (RRMS), results from the MIST clinical trial show. The study “Effect of Nonmyeloablative Hematopoietic Stem Cell Transplantation vs Continued Disease-Modifying Therapy on Disease Progression…

January 15, 2019 News by Jose Marques Lopes, PhD

Ocrevus Targets Certain T-Cells, Along with B-Cells, in MS Patients, Study Reports

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.

January 14, 2019 News by Jonathan Grinstein

Tecfidera Effective in East Asian RRMS Patients, Phase 3 Trial Shows

Tecfidera (dimethyl fumarate) demonstrated strong efficacy in Japanese and other East Asian patients with relapsing-remitting multiple sclerosis (RRMS), a Phase 3 clinical trial shows. These results are consistent with previous clinical trials, which included mostly white MS patients, and show that Tecfidera can also be effective across various other patient demographics. Findings of the trial were reported in the study, “A randomized placebo-controlled trial of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis from East Asia and other countries,” in the journal BMC Neurology. Tecfidera, a delayed-release dimethyl fumarate capsule, marketed by Biogen, is an oral therapy approved in many parts of the world for the treatment of RRMS. In previous Phase 3 clinical studies, DEFINE (NCT00420212), and CONFIRM (NCT00451451), Tecfidera showed substantial effectiveness on clinical and neuroradiological measures in RRMS patients. The study participants were predominantly white (79% in DEFINE and 84% in CONFIRM), and there were 10% or fewer East Asian patients. In general, very little data is available on Tecfidera's effectiveness in East Asian MS patients. In this APEX Part 1 (NCT01838668) trial, researchers from the Kansai Medical University in Japan and Biogen evaluated the safety and efficacy of Tecfidera over 24 weeks (six months) in the treatment of RRMS patients from East Asia and other countries. Participants with active MS between the ages of 18 and 55, with ethnic origins in Japan, South Korea, or Taiwan were included. To compare East Asian and white MS patients, study enrollment was expanded to patients from Eastern Europe (Czech Republic and Poland). In all, the six-month, double-blind, placebo-controlled study recruited 225 patients, 142 of whom were East Asian (63.4%). It was completed by 213 participants. Patients were randomly assigned to receive Tecfidera, (240 mg, twice daily) or a matching placebo for six months. They were assessed at the beginning of the study, at three months, and again at six months. They underwent MRI (magnetic resonance imaging) scans for neurological examination, in addition to routine health checks. The primary objective of the study was the total number of new inflammatory lesions on brain MRI scans from three to six months. Secondary goals included the number of specific new, or newly enlarging T2 hyperintense lesions — lesions reflective of damage to nerve cell connections — from the beginning of the study to six months. Tertiary goals included standard safety measurements, and annualized relapse rate over six months. “We chose radiological measures to serve as primary and secondary endpoints, due to the ability of MRI to detect lesions that might not produce clinical manifestations in the short-term,” the researchers wrote. Results showed that Tecfidera treatment significantly reduced (84%) the total number of new MRI lesions from weeks 12 to 24 (primary objective), compared with placebo — specifically by 85% in the Japanese subgroup, 81% in the total East Asian subgroup, and 87% in the Eastern European subgroup. Regarding the trial's secondary objective, the total number of new MRI lesions from the beginning of the study up to six months was reduced by 75% in the Tecfidera group (78% in the Japanese, 76% in the East Asian, and 73% in the Eastern European subgroups), and the mean number of new/newly enlarging T2 hyperintense lesions was reduced by 63% in the Japanese, and 58% in the East Asian subgroups, compared with placebo. Most patients reported one or more adverse events (77% in the placebo group and 86% in the Tecfidera group). Most adverse events were mild or moderate in severity, and the ones affecting patients taking Tecfidera either related mainly to flushing symptoms or to gastrointestinal problems. The team concluded that the "results suggest that the strong efficacy and favorable benefit-risk profile of [Tecfidera] extends to Japanese and other East Asian patients with MS." The second part of the ongoing clinical trial, APEX Part 2, is an open-label extension trial — where both the researchers and participants know which treatment they are getting — designed to further examine the long-term safety and tolerability of Tecfidera in East Asian MS patients.

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