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Initial treatment of relapsing-remitting multiple sclerosis (RRMS) with Gilenya (fingolimod), Tysabri (natalizumab), or Lemtrada (alemtuzumab) is associated with a lower risk of conversion to secondary progressive multiple sclerosis (SPMS), compared with interferon beta or Copaxone (glatiramer acetate), a study reports. Findings also showed that…

An international survey of caregivers and adults with neurological diseases, including multiple sclerosis (MS), revealed that spasticity is a hidden burden, having a negative effect on the ability to perform everyday tasks, and that relieving its symptoms significantly improves patients’ quality of life. The survey was presented by…

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…

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.

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…

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.

Multiple sclerosis (MS) experts in the United Kingdom have proposed consensus guidelines for the management and treatment of pregnant women with the disease, and couples affected by MS who are planning a pregnancy. The new guidelines are expected to reduce uncertainty about treatments that are considered to be safe and…

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.

Dozens of films have focused on those with diseases or disabilities — and there’s no shortage of Hollywood productions about love and sex. But only a handful have ever really tried to combine these two themes. “Take a Look at This Heart” does the job with tenderness and finesse.

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…

WeHealth by Servier and PathMaker Neurosystems have established a new partnership to develop and commercialize the first neuromodulation technology for noninvasive treatment of spasticity, the companies announced. The agreement establishes an exclusive worldwide distribution arrangement, except for the U.S. and Japan, for PathMaker’s MyoRegulator. The MyoRegulator uses two pairs of…

Australia was one of the first countries to approve the use of Mavenclad (cladribine tablets, 10 mg) to treat patients with highly active relapsing-remitting multiple sclerosis (RRMS). Now, the country’s government has taken another step to ensure this 20-day course treatment is available to the largest number possible of people affected by the disease. Australia’s Prime Minister, Hon. Scott Morrison MP, announced that Merck KGaA’s therapy was included on the Pharmaceutical Benefits Scheme (PBS) listing effective Jan. 1. This will make Mavenclad affordable for about 6,200 patients each year who are already accessing PBS-subsidized medicines for MS. (Of note, Merck KGaA is known as EMD Serono in the U.S. and Canada.) This was made possible by the joint effort of MS Australia, MS Research Australia, clinicians and members of the MS community who, after successive submissions, achieved a positive recommendation by the Pharmaceutical Benefits Advisory Committee (PBAC) to list Mavenclad on PBS as a treatment for RRMS. Australia's government will cover almost all costs of Mavenclad, which will mean that patients will have to pay only $40.30 per prescription, or $6.50 for concessional patients. “Thanks to our strong economic management, we’ve ensured that every new, essential medicine recommended for listing by the Pharmaceutical Benefits Advisory Committee receives government subsidy to make it affordable for all Australians,” the Prime Minister said in a press release. Mavenclad was developed to target immune T- and B-cells that trigger relapsing MS without suppressing the entire immune system. To be taken for a maximum of 20 days over two years, the oral drug has shown it helps MS patients remain relapse-free for up to four years, while supporting the “reset” of the immune system. Australia's regulatory agency decided to approve Mavenclad based on the findings of a number of clinical trials, including the Phase 3 CLARITY (NCT00213135), CLARITY EXTENSION (NCT00641537), and ORACLE-MS (NCT00725985) studies, as well as the Phase 2 trial ONWARD study (NCT00436826), and the long-term PREMIERE (NCT01013350) trials. These clinical studies involved more than 2,700 RRMS patients, some of whom were followed for more than 10 years. Overall, the trials showed that Mavenclad significantly reduced relapse rates, disability progression, and brain atrophy. Doctors recommend the therapy for patients who failed to respond to, or are unable to tolerate, other MS treatments.

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…

Five finalists remain in the running for the $1 million prize being offered in the Mobility Unlimited Challenge, a global competition to promote the development of innovative solutions for personal mobility devices. A panel of expert judges selected the finalists from among 80 applications submitted by teams from 28 countries.

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…

Biogen announced the start of a global Phase 3b clinical trial to evaluate the efficacy and safety of extended interval dosing (EID) with Tysabri (natalizumab) in patients with relapsing-remitting multiple sclerosis (RRMS). Results of the six-week dosing interval will be compared with the approved standard interval dosing…

Because multiple sclerosis (MS) presentation and progression course can be very different between people of African ancestry and Caucasians, the recruitment of minorities to Phase 3 clinical trials is of particular importance. Researchers in the MS field and the general MS community should make a greater effort to improve…

Lowering body temperature helps to improve exercise and functional capability in multiple sclerosis (MS) patients by preventing disease worsening, researchers in  Greece report. The study with that finding, “Impact of pre-cooling therapy on the physical performance and functional capacity of multiple sclerosis patients: A systematic review,” was published in…

Banner Life Sciences has received tentative approval from the U.S. Food and Drug Administration (FDA) for its new drug application (NDA) for Bafiertam (monomethyl fumarate), a novel bioequivalent of Biogen’s Tecfidera (dimethyl fumarate) for the treatment of relapsing-remitting multiple sclerosis (RRMS). Final approval is expected no later than…

An altered metabolism and signaling is associated with the ability of a subset of immune T helper 17 (Th17) cells to induce neuroinflammation, according to a new study of mice. The findings may lead to new treatments for multiple sclerosis (MS) and other chronic inflammatory diseases, the scientists said.

Unusually high levels of a transcription factor called paired related homeobox protein 1 (PRRX1) in human oligodendrocyte progenitor cells hinders their ability to respond to the loss of myelin and to transform into mature, myelin-producing oligodendrocytes, a new study shows. These findings suggest a new potential way of treating …

A product called acrolein, which is naturally excreted by the body and possible to measure in urine and blood, may be a potential biomarker to help diagnose and evaluate disease activity in people with multiple sclerosis (MS), according to preliminary research in animal models and humans. Researchers are investigating whether acrolein…

Multiple Sclerosis News Today brought you daily coverage of key findings, treatment developments, and clinical trials related to multiple sclerosis (MS) throughout 2018. We look forward to reporting more news to patients, family members, and caregivers dealing with MS during 2019. Here are the top 10 most-read articles of…