The loss of immune B-cells, and the resulting changes in the profile of immune T-cells, is a major mechanism of action for the beneficial effects seen with ublituximab treatment in multiple sclerosis (MS) patients, a study suggests. B-cells are a type of immune cell best known for producing…
research
People with pediatric-onset multiple sclerosis (POMS) have a greater decline in cognitive function, and are more likely to experience cognitive impairment in adulthood, than those whose disease began when they were adults, a study reports. The study, “Long-term Cognitive Outcomes in Patients With Pediatric-Onset vs Adult-Onset…
Treatment with Sanofi Genzyme’s Lemtrada (alemtuzumab) for up to two years lowers the levels of serum neurofilament light chain (sNfL), a proposed biomarker of nerve damage, in relapsing-remitting multiple sclerosis (RRMS) patients to levels comparable to those seen in healthy people, data from the CARE-MS I study shows. Lemtrada’s effectiveness…
Immune system activation induced by filgrastim may be beneficial for patients with progressive multifocal leukoencephalopathy associated with the use of Tysabri (natalizumab), without worsening multiple sclerosis (MS) progression, a study says. The study with that finding, “Treatment of natalizumab‐associated PML with filgrastim,” was published in…
Deferiprone, a compound that lowers iron levels in the bloodstream by binding to iron molecules, can slow progression of a severe neurodegenerative disorder called pantothenate kinase-associated neurodegeneration (PKAN), a study reports. Because a toxic buildup of iron in the brain is also associated with multiple sclerosis and other neurological…
DELIVER-MS Trial Recruiting RRMS Patients to Help Improve Treatment Decision-making What’s the best way to attack multiple sclerosis when it’s first diagnosed? Do you hit it hard and fast using the most effective disease-modifying therapy (DMT), or do you start with a lower efficacy DMT and slowly ramp up?…
The relative risk of developing cancer was found to be higher in multiple sclerosis (MS) patients who more frequently switched between disease-modifying treatments, according to a study. In addition, researchers found an increased incidence of cancer in male MS patients from 20 to 50 years old, and in female…
Human Blood-brain Barrier in a Chip, Created in the Lab, May Help Design New Therapies, Study Shows
By tweaking stem cells in a laboratory, researchers were able to generate a model of the human blood-brain barrier (BBB) in a chip. The BBB is a highly selective barrier that is damaged in multiple sclerosis (MS), allowing immune cells to reach the central nervous system and damage…
A new artificial intelligence (AI)-based model is better than conventional methods for detecting brain changes in response to treatment with Tysabri (natalizumab) in patients with relapsing-remitting multiple sclerosis (RRMS), a study reports. The study, “High-dimensional detection of imaging response to treatment in multiple sclerosis,” was published in…
A mismatch — between the ancestral immune function changes induced by the placenta and fewer modern-day pregnancies — may help explain the greater risk for multiple sclerosis (MS) and other autoimmune diseases in women in industrialized societies, according to a new study. The shift toward a sedentary lifestyle may…
New research suggests that rising blood pressure might be predictive of intracranial hemorrhage — bleeding in the brain, a serious and sometimes fatal condition — in people with multiple sclerosis (MS) who are receiving treatment with Lemtrada (alemtuzumab). The study, titled “Intracerebral haemorrhage during…
Startup company Oscine Therapeutics has received an investment from Sana Biotechnology to support the research and development of cell-based therapies for a variety of neurological disorders, including multiple sclerosis (MS). This venture is based on work done over the past several decades in the lab of Steve…
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…
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…
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…
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 Licenses Mini-Brain Technology, Which May Speed Therapy Discovery for Neurological Diseases
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…
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…
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…
When I think of multiple sclerosis and falls, I tend to think about people who are upright and walking when it happens. I hadn’t considered the risks for people who spend most of their waking hours using a wheelchair or a scooter. Many studies have looked at people with MS…
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”…
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