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Aubagio (teriflunomide), an approved medicine for relapsing forms of multiple sclerosis (MS), specifically targets highly metabolic and more autoreactive T-cells, analysis of the Phase 3 TERI-DYNAMIC clinical trial data shows. The findings, contrary to expectations, support a selective effect of Aubagio on different T-cell populations. The study “Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects” was published in the Science Translational Medicine journal. In MS, immune cells, or lymphocytes known as T-cells, attack and destroy myelin, the fat-rich substance that wraps around nerve fibers (axons). Myelin loss creates lesions that affect nerves of the brain and spinal cord. Previous evidence suggested that T-cells, depending on their active or resting state, rely on specific ways of energy production or metabolism. Aubagio, marketed by Sanofi Genzyme, is a well-known inhibitor of a mitochondrial enzyme called dihydroorotate dehydrogenase (DHODH), that is crucial for the activity of T-cells. However, how Aubagio selectively targets the autoreactive T-cells is poorly understood. To shed light on this matter, an international group of researchers used data from the TERI-DYNAMIC clinical trial that tested Aubagio in patients with relapsing form of MS to better understand how the therapy inhibited the patients' self-immune responses. The Phase 3, open-label TERI-DYNAMIC trial (NCT01863888) included 70 patients from Belgium, Germany, and The Netherlands, aged 18 to 56. Participants received Aubagio as a 14 milligram (mg) once-daily, oral dose, and researchers assessed the changes in immune cells' profile up to 24 weeks. Results showed that, contrary to what was expected, Aubagio was not generally decreasing T-cell levels in treated patients. Instead, it significantly reduced a particular subset of T-cells, called "Th1 helper cells." Moreover, researchers found that the diversity of T-cell receptors — the surface proteins that can recognize a particular antigen (a protein that can elicit an immune response) — making T-cells specific to a certain target was reduced in MS patients after treatment with Aubagio. These findings suggested that some T-cells were particularly susceptible to Aubagio. Using a mouse model for MS, the experimental autoimmune encephalomyelitis (EAE) model, researchers showed that the CD4+ T-cells (helper T-cells) and CD8+ T-cells, those that reacted most strongly against self-antigens, were the most sensitive to DHODH inhibition by Aubagio. Moreover, researchers saw that Aubagio was not affecting the production of pro-inflammatory molecules — called cytokines — at the cell level, but their overall decrease probably was due to the reduction in T-cell numbers. In line with these findings, CD4+ T-cells that produced the cytokine interferon gamma were significantly reduced with Aubagio treatment, whereas CD4+ T-cells that produced interleukin 17A were unchanged. This suggests that Aubagio is able to interfere with specific sub-types of immune cells. When the team compared the metabolic profile of T-cells from healthy subjects with that from patients with relapsing-remitting MS (RRMS) in both remission and in relapse phases, they found that the metabolism of T-cells from the last group was significantly altered, and thus targetable. Altogether, the results suggested that T-cells with a high-affinity to self-antigens are more susceptible to inhibition of the DHODH enzyme by Aubagio. “Therapeutic targeting of metabolic alterations might represent an attractive concept in MS, and might represent an as yet unrecognized key mechanism of teriflunomide-mediated immune modulation in this disease,” the researchers concluded.

Scientists are zeroing in on mutations in a few genes that appear to be major risk factors for developing multiple sclerosis (MS). The results of their research suggest there are common biological pathways that cause the disease. The study, “Exome sequencing in multiple sclerosis families identifies 12…

Exosomes — tiny vesicles secreted by cells — collected from bone marrow stem cells and injected into a mouse model of multiple sclerosis (MS) helped to treat the disease, a study reports. Specifically, this treatment eased myelin loss and neuroinflammation in the mice, and improved motor function, the…

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) both agreed to review for possible approval ozanimod, Celgene‘s investigational oral therapy for relapsing forms of multiple sclerosis (MS). An FDA decision on the company’s New Drug Application for ozanimod is expected on…

Obesity, altered lipid (fat) levels, and elevated leptin — an hormone produced by fat cells — may contribute to neuroinflammation, and worse disease severity in people with relapsing-remitting multiple sclerosis (RRMS), research has found. A study with the findings, titled “Obesity worsens central inflammation and disability in multiple…

A study found no genetic risk factors associated with vitamin D in families with a history of multiple sclerosis (MS), suggesting that the link between vitamin D deficiency and MS risk is determined by environmental factors rather than a genetic predisposition. The study “Exonic variants of genes related…

Sutter Health, a California-based healthcare group, has partnered with the biotechnology company Roche to test a new mobile app that aims to improve monitoring of symptoms in people who have multiple sclerosis (MS). The app, called Floodlight, “may give neurologists access to meaningful, actionable patient data to…

The pro-inflammatory protein interleukin-17 (IL-17) drives inflammation by promoting a chemical modification, called phosphorylation, in the RNA molecule of the regnase-1 enzyme, a mouse study shows. These findings support the development of therapeutics that block the phosphorylation of regnase-1 to halt IL-17-mediated inflammation, as seen in multiple…

In partnership with @Point of Care, the Multiple Sclerosis Association of America (MSAA) is offering a comprehensive educational video series about multiple sclerosis (MS). The concise, 12-part series — titled “Understanding Multiple Sclerosis” —  features neurologist and MS expert Michelle T. Fabian, MD, and covers…

Vumerity (diroximel fumarate), taken as a 462 milligram (mg) tablet twice daily, significantly decreases disease activity in patients with relapsing-remitting multiple sclerosis (RRMS), and leads to low rates of gastrointestinal side effects, new interim data of Phase 3 trial EVOLVE-MS-1 show. The findings were presented at the 2019 Consortium…

AxoSim has acquired exclusive rights to lab-grown brain miniatures, coined “Mini-Brain,” a technology developed at Johns Hopkins University that uses stem cells to create models of the human brain in a dish. This technique may help speed therapy discovery for many neurological diseases, including multiple sclerosis…

Mavenclad (cladribine) may surpass Gilenya (fingolimod) in the category of oral disease-modifying therapy (DMT) of choice for the treatment of multiple sclerosis (MS) in Canada, according to a press release. The Canadian healthcare market for MS has grown considerably over the past two years. In November…

EMD Serono is supporting World MS Day, an initiative created by the Multiple Sclerosis International Federation (MSIF) to promote solidarity and raise awareness about multiple sclerosis (MS) worldwide, by joining efforts to make the disease more “visible.” Known as Merck KGaA…

Targeting the excessive activation of immune cells called neutrophils, and the associated oxidative stress, may be a therapeutic strategy in patients with multiple sclerosis (MS), according to a mouse study. The study, “Deficiency of Socs3 leads to brain-targeted EAE via enhanced neutrophil activation and ROS production,” was…

Cyxone submitted an application to the Netherlands research ethics committee to start the first clinical trial in humans testing T20K, its investigational preventive treatment for multiple sclerosis (MS). Approval by the Netherlands regulating authority…

The Multiple Sclerosis International Federation (MSIF) is encouraging family members, caregivers, and patients affected by multiple sclerosis (MS) to participate in World MS Day today. Created by MSIF and its members in 2009 to promote solidarity and bring hope to those affected by MS, the global initiative takes…

The Multiple Sclerosis (MS) Society of Canada closed its celebration of multiple sclerosis (MS) Awareness Month by launching the Acts of Greatness campaign that aims to raise $75 million to support research about the disease. The campaign was activated May 24 with the placements of five-meter decals…

Biopharmaceutical company Celgene has teamed up with the Multiple Sclerosis Association of America (MSAA) to launch a new initiative called MS MindShift: A New View of MS, aimed at educating the multiple sclerosis (MS) community on brain health. Although it’s an “important topic,” brain health “is not…

Corrona has expanded its collaborative multiple sclerosis (MS) U.S. patient registry to include Genentech, the first pharmaceutical company to participate. Established in 2017, the Corrona MS Registry is a real-world U.S.-based registry, developed in collaboration with the National MS Society. Its goal is to help guide treatment decisions based on…

The International Pediatric Multiple Sclerosis Study Group (IPMSSG) has updated its guidelines regarding the participation of children and adolescents with multiple sclerosis (MS) in clinical trials. The new series of guidelines were published recently in Neurology, the journal of the American Academy of Neurology (AAN), in an article titled…

The latest research in multiple sclerosis (MS), along with the most recent advancements in treatment strategies and comprehensive care, will be presented at the Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, which beings today. Running through June 1 at the Washington State Convention Center in Seattle, the…

The first patient has been dosed in a Phase 2B clinical trial evaluating the safety, efficacy, and tolerability of SAR442168 in people with relapsing multiple sclerosis (MS). SAR442168, formerly known as PRN2246, is being developed by Principia Biopharma, in collaboration with Sanofi Genzyme, for MS and other central nervous…

MC10 and AbbVie are working together to launch clinical trials exploring the use of BioStamp nPoint, a system of wearable sensors that collects health data from multiple sclerosis (MS) patients, to determine if the information may serve as meaningful measures for clinical studies. MC10’s BioStamp…

Stress-induced changes in gut bacteria, or gut microbiota, may play a significant part in the possible link between exposure to stress and the risk of autoimmune disorders such as multiple sclerosis (MS), a mouse research study says. In the study “…

Early, positive safety results from a Phase 1 trial testing a potential immunotherapy, ATA188, in people with progressive multiple sclerosis will be detailed at the 5th Congress of the European Academy of Neurology (EAN) late next month, its developer, Atara Biotherapeutics, announced. ATA188 is an investigational and “off-the-shelf”…

Reactivation of ancient viruses incorporated into the human genome in the course of evolution may be involved in the acute inflammatory response that is characteristic of multiple sclerosis (MS), a study says. The findings of the study, “Expression of endogenous retroviruses reflects increased usage of atypical enhancers in…

Simvastatin, a widely prescribed statin that works to lower cholesterol levels, may slow brain atrophy and disease progression in people with secondary progressive multiple sclerosis (SPMS) for reasons unrelated to changes in blood cholesterol, a new analysis of a Phase 2 clinical trial reports. These findings are in…

Vesicles in the blood that contain a protein called fibrinogen important for blood clotting were found to be “sufficient and required” for the occurrence of spontaneous disease relapses in mouse models of multiple sclerosis (MS), a study reports. In mice, these vesicles were associated with immune cell infiltration, inflammation,…

EMD Serono, the biopharmaceutical division of Merck KGaA in the U.S. and Canada, announced the launch of the company’s Multiple Sclerosis Leadership and Innovation Network (MS-LINK), an interdisciplinary research community aimed at improving the care of individuals with multiple sclerosis (MS). The program will combine clinical outcomes…

Pear Therapeutics, in collaboration with Novartis, has launched a study evaluating the clinical use of Pear-006, its software-based prescription digital therapeutics (PDT) product for treating depression symptoms in people with multiple sclerosis (MS). PDTs belong to a new class of treatment strategies in healthcare intended to treat diseases,…