Jose Marques Lopes, PhD, science editor —

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…

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…

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…

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.

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.

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…

Pretreating multiple sclerosis patients with antihistamines more extensively and with hydration can significantly reduce — by 60% — the likelihood of infusion-associated reactions that are the most common side effect of Ocrevus (ocrelizumab) use, a pilot study reported. Data also found that older and male MS patients are less likely to have…

Aubagio (teriflunomide) has become the first once-a-day, oral disease-modifying therapy (DMT) for multiple sclerosis (MS) to be approved for use in India. Sanofi Genzyme’s therapy is indicated for first-line treatment of relapsing MS. It should be taken each day with or without food, and patients in India will have…

Palliative care in a hospital setting rose 30 fold among multiple sclerosis (MS) patients in the U.S. from 2005 to 2014, and was associated with longer hospital stays and greater numbers of in-hospital deaths but also lower overall costs, according to a large data study. Increased reliance on such care…

Patients with relapsing-remitting multiple sclerosis (RRMS) on Rebif (interferon beta 1-a), using the RebiSmart autoinjector, have high treatment adherence, despite seasonal weather or temperature fluctuations, as well as fewer relapses over one year, a real-world study reports. The study, “Seasonal adherence to, and effectiveness of,…

Assessing changes in a person’s heart rate can help to predict the degree to which lymphocyte numbers will decrease in relapsing-remitting multiple sclerosis (RRMS) patients using Gilenya (fingolimod), according to a small study. The research, “Fingolimod-induced decrease in heart rate may predict subsequent decreasing degree of…

Multiple sclerosis patients of working age who are unemployed or on a reduced work schedule are likely to show considerable cognitive impairment on tests, especially those measuring mental processing speeds, than patients who are more gainfully employed, a review study reports. This link held true even in patients with little…

Treating primary progressive multiple sclerosis (PPMS) patients with Ocrevus (ocrelizumab) can help to preserve strength and function in their hands and the arms, analysis of data from a Phase 3 trial found. The research, “Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive…

Appropriate control of immune B-cell numbers and activation in the nervous system is key to preventing inflammation in multiple sclerosis (MS), according to a study. These findings also showed that patients with higher levels of a specific B-cell-regulating cell type had less disease activity. The study, “…

The ability to track multiple sclerosis (MS) at any time, gain a more complete picture of each patient’s disease course and a better understanding of MS are among the possible benefits of the FLOODLIGHT app, according to Laura Julian, PhD, principal medical science director at Genentech. The company…

Denali Therapeutics and Sanofi will collaborate to develop a compound called DNL747 that may treat multiple sclerosis (MS) and other neurodegenerative disorders. The companies will also jointly work on the development of a separate possible therapy, DNL758, for systemic inflammatory diseases such as rheumatoid arthritis and psoriasis. Both DNL747 and DNL758…

Multiple sclerosis (MS) treatment Tecfidera (dimethyl fumarate) binds to a specific amino acid in key enzymes to inhibit their activity, according to a study that sheds more light on this therapy’s little-known mechanism of action. This newly identified regulatory mechanism may lead to the discovery of new compounds…

Treating patients with primary progressive or relapsing multiple sclerosis (MS) early with Ocrevus (ocrelizumab) is key to slowing disease progression, according to Hideki Garren, global head of Multiple Sclerosis and Neuroimmunology at Genentech. In an interview with Multiple Sclerosis News Today at the recent 34th congress of the European Committee for Treatment…

Environmental changes, such as high temperatures and alterations in salt types and concentrations, trigger structural changes to myelin that may increase the risk of multiple sclerosis (MS), according to a new study. The research, “Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions,” was…

Tailored, highly effective therapies early in the disease’s course may be a way forward in multiple sclerosis (MS) treatment, according to Cleveland Clinic neurologist Robert Bermel. Another neurologist with the Cleveland Clinic, Robert Fox, talked about potential and upcoming progressive MS treatments.  In interviews with Multiple Sclerosis News…

Treating relapsing-remitting multiple sclerosis (RRMS) patients with GeNeuro’s investigational compound GNbAC1 lessened brain atrophy and lesion load and suggested myelin preservation, according to results of a Phase 2b study. Importantly, monthly intravenous GNbAC1 administration for 48 weeks also had neuroprotective effects in the study’s inactive population, which refers…

Despite its lack of specificity to multiple sclerosis (MS) in particular, monitoring patients with a blood biomarker — serum neurofilament light (sNfL) — may hold promise as a relatively easy way to assess treatment response and brain damage, according to MS experts. But there’s considerable work still to be…

Measuring the blood level of neurofilament light chain (NfL) may predict brain shrinkage in primary progressive (PPMS) and secondary progressive multiple sclerosis (SPMS), according to a new study. The findings also show that NfL levels are associated with brain lesion load in these patients. The research, “…

Treatment with autologous hematopoietic stem cell transplant (aHSCT) led to a safe and rapid lessening of disability and no clinical relapses in patients with aggressive multiple sclerosis (MS), according to a new study. The research, “The use of autologous hematopoietic stem cell transplantation as a…

Advances in multiple sclerosis research and the development of new treatments over the last several decades give sustained reasons for hope as continue moving toward our future, according to Jerry S. Wolinsky, a neurologist and MS specialist whose career spans more than 40 years. In a wide-ranging interview with Multiple…

Treatment of relapsing-remitting multiple sclerosis (RRMS) patients with Tecfidera (dimethyl fumarate) is associated with fewer new brain lesions at two years, lower relapse rates, increased time to first relapse, and reduced treatment discontinuation than with Aubagio (teriflunomide), according to a nationwide study from France and a real-world, population-based…

Up to half of women with multiple sclerosis (MS) who stop treatment with Gilenya (fingolimod) when planning to become pregnant will experience a relapse during pregnancy, according to a new study. The findings also revealed relapses over the first six months after giving birth in a quarter of…

Levels of proposed biomarker neurofilament light chain (NfL) are associated with therapeutic effects of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (RRMS) patients, according to a real-world study. Study findings also revealed that treatment with either Lemtrada (alemtuzumab, marketed by Sanofi Genzyme), Gilenya (fingolimod, marketed by Novartis), Tecfidera (dimethyl fumarate, marketed…

Relapsing-remitting multiple sclerosis (RRMS) patients with serum neurofilament light chain (sNfL) levels higher than a proposed threshold have a higher risk of disease activity, and worsened disability, lesions and brain shrinkage in the long term, according to a new study. The research, “Serum neurofilament light (NfL)…