March 2, 2020 News by Ana Pena PhD #ACTRIMS2020 – Vitamin D at High Dose Can Worsen MS, Early Study Says High-dose vitamin D supplements appear to aggravate inflammation and myelin loss in the brain and spinal cord, and worsen the disability associated with multiple sclerosis (MS), a study in a mouse disease model reported. Excessive use of vitamin DĀ causes calcium levels to…
February 27, 2020 News by Forest Ray PhD Cellular Metabolism Could Be New Therapeutic Target in MS, Study Suggests Immune system cells can either trigger or suppress inflammation by controlling mitochondrial respiration ā the process that occurs in mitochondria, the cells’ powerhouses, and results in the production of usable energy by cells ā according to a recent study. This discovery raises the possibility that…
February 20, 2020 News by Joana Carvalho, PhD Bone Marrow Transplant Can Replace Overactive Immune Cells, Preventing Inflammation in MS, Study Says A bone marrow transplant can remove the majority of overactive immune T cells from the central nervous system (CNS) in patients with active relapsing-remitting multiple sclerosis (RRMS), allowing the body to replace them with healthy ones, a study has found. This opens up new treatment avenues to…
February 12, 2020 News by Steve Bryson, PhD Gilenya Works to Treat RRMS by Specifically Targeting B-cells and T-helper Cells, Study Finds Treating people with relapsing-remitting multiple sclerosis (RRMS) for one year with the immune-modulating therapy Gilenya (fingolimod)Ā reduced the numbers of antibody-producing B-cells and of T helper cells, a study finds.Ā While the…
February 6, 2020 News by Patricia Inacio, PhD Interleukin-17A Plays Key Role in Inflammation in MS, Mouse Study Finds The immune signaling molecule interleukin-17A (IL-17A) promotes the recruiting of inflammatory cells to the central nervous system (brain and spinal cord) in a multiple sclerosis (MS) mouse model, a study found. The findings support the potential of therapies that target IL-17 in MS. IL-17A is part of the IL-17…
February 6, 2020 News by Vanessa Pataia Dietary Changes May Delay Development and Progression of MS, Study Finds Changing a person’s diet to reduce the amount of methionine (amino acid found in food) could delay the development and progression of inflammatory and autoimmune disorders, includingĀ multiple sclerosis (MS). That finding was described in the study ā…
February 4, 2020 News by Patricia Inacio, PhD Cerebrospinal Fluid of MS Patients More Diverse and Filled with Pro-Inflammatory Cells, Study Shows People with multiple sclerosis (MS) have a more diverse set of immune cells in their cerebrospinal fluid (CSF), the fluid that bathes the central nervous system, but no such diversity is seen in their blood, a study reports. Instead, MS causes changes in the activation of immune cells in…
January 24, 2020 News by Patricia Inacio, PhD Mayzent Helps Regulate the Immune System in SPMS, Study Shows Mayzent (siponimod), an approved oral therapy for activeĀ secondary progressive multiple sclerosisĀ (SPMS), promotes a more regulatory immune system, which may explain its added benefits for SPMS, new clinical data show. The study āSiponimod enriches regulatory T and B lymphocytes in secondary progressive multiple sclerosisā was published in the…
January 7, 2020 News by Marta Figueiredo, PhD Probiotics Show Potential to Prevent, Delay Development of MS, Study Finds Probiotics show potential to prevent and delay the development of multiple sclerosis (MS) by changing immune and inflammatory responses, according to a review study. Data further support the link between the gutāsĀ microbial community (microbiota) and the central nervous system (brain and spinal cord), and neurodegenerative diseases. However, large-scale clinical…
December 6, 2019 News by Joana Carvalho, PhD Signaling Protein of Intestines May Trigger Nervous System Inflammation in MS, Study Says A signaling protein (Smad7) that usually blocks the activity of a molecule called transforming growth factor-beta (TGF-Ī²) appears to be overactive in people with multiple sclerosis (MS), leading to the activation and migration of immune cells from the intestine to the central nervous system, a study reports. The study,…
November 25, 2019 by Ana Pena PhD Protein That Helps Cells Break Down Sugar Also Promotes Inflammation, Study Suggests A protein involved in cell metabolism, called PKM2, was found to be central to switching ‘on’ immune cells that play critical roles in inflammatory and autoimmune diseases such as multiple sclerosis (MS), an early study reports. Blocking the activity of PKM2 (pyruvate kinase M2) eased MS-like symptoms…
October 28, 2019 News by Marisa Wexler, MS AP-1 Transcription Factor Family is Critical for Healthy T-cell Development, Study Says The transcription factor family AP-1 is crucial for the proper activation of immune T-cells, a new study shows, and this finding may have important implications for autoimmune diseases such as multiple sclerosis. The study, titled “AP-1 activity induced by co-stimulation is required for chromatin opening during…
October 8, 2019 News by Patricia Inacio, PhD Targeting Toxic T Helper Cells – Those with CXCR6 Receptor – Seen to Prevent MS in Mouse Model Targeting the chemokine receptor CXCR6, a protein at the surface of a certain group of T helper cells, preventedĀ the development of multiple sclerosis (MS) in a mouse model of the disease, a study reports. Its findings suggest that antibodies targeting T helper cells ā known drivers of MS ā…
September 30, 2019 News by Alice MelĆ£o, MSc Trigger for MS and Other Immune Diseases May Be T-cells in Early Activation State, Study Reports A specific type of immune cell in a particular activation state is linked to such immune diseases as multiple sclerosis (MS) and inflammatory bowel disease (IBD), a collaborative research study found. Disease-associated genetic variants ā changes in DNA sequences or mutations in genes ā can affect the response of immune…
September 9, 2019 News by Marta Figueiredo, PhD Inflammation Hijacks Myelin Repair Cells to Promote Immune Attacks, Study Shows Brain inflammation in multiple sclerosisĀ (MS) hijacks immature myelin repair cells, not only preventing myelin restoration but also promoting sustained inflammation and immune attacks against myelin, a preclinical study shows.
September 4, 2019 News by Marta Figueiredo, PhD Targeting Inflammatory Th17 Cells to Slow MS Disability Possible with Fewer Side Effects, Study Suggests Scientists may have found a way to manipulate T-helper 17 (Th17) cells so as to lower their ability to trigger inflammation, delaying the onset ofĀ multiple sclerosisĀ (MS) in a mouse model and slowing its progression without affecting the entire immune system. Their findings may lead to new treatments with fewer…
August 22, 2019 News by Alejandra Viviescas, PhD Gene on X Chromosome May Be Reason Women at Higher Risk of MS, Study Says Females of certain species ā like humans and mice ā have a known ability to produce more of the geneĀ Kdm6aĀ than males because it’s located on the X chromosome, of which females have two.Ā Kdm6aĀ is also quite active in immune system T-cells, a study found, and silencingĀ it in a mice model…
August 9, 2019 News by Jose Marques Lopes, PhD Harnessing T-cell Subtype May Suppress Immune Responses in MS, Study Suggests Though known mainly for killing tumor and virally infected cells, a T-cell subtype may restrain immune responses and be protective in autoimmune diseases such as multiple sclerosis (MS), according to new research. The study, āOpposing T cell responses in experimental autoimmune encephalomyelitis,ā was published recently in…
July 25, 2019 News by Ana Pena PhD Abundant T-helper Cells Evident in MS Patients May Cause Inflammation, Study Reports Scientists identified and “fingerprinted” a group of T-helper cells that are unusually numerous in the blood and central nervous system of people with relapsing-remitting multiple sclerosis (RRMS), and may be the reason behind the neuroinflammation seen in these patients. This T-cell population carries specific markers involved in the transmission…
July 22, 2019 News by Jose Marques Lopes, PhD Microbes in Gut Protect Nervous System After Viral Infections, Study Suggests Gut microbes prime immune cells called microglia to protect the brain and nervous system from neurological damage due to viral infections, according to new research in mice. The findings suggest that maintaining a healthy and diverse microbiota ā the population of bacteria, fungi, and viruses within the body, especially the…
July 11, 2019 News by Patricia Inacio, PhD Targeting Oct1 Protein in T-cells Might Prevent Autoimmune Reactions, MS Mouse Study Finds Targeting a protein found in immune T-cells called Oct1 may help prevent the misguided immune response seen in autoimmune diseases like multiple sclerosis (MS), a study shows. Most importantly, a lack of Oct1 does not influence the immune systemās ability to fight viral infections. The study āT cell-selective…
July 10, 2019 News by Jose Marques Lopes, PhD MS Brain Lesions Linked to Early-life Viral Infection in Mice, Way of Blocking Inflammatory Spread Seen An experimental treatment known as OB-002, that works to block an inflammatory molecule in the brain, prevented the development of lesions there after an early-in-life viral infection in a mouse model of multiple sclerosis (MS). The research āBrain-resident memory T cells generated early in life…
June 20, 2019 News by Marisa Wexler, MS Potential Mechanism Behind Effectiveness of B-cell Depletion Therapy in MS Uncovered 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…
June 11, 2019 News by Patricia Inacio, PhD Aubagio Targets Highly Metabolic Auto-reactive T-Cells, Study Shows AubagioĀ (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 āTeriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effectsā was published in the Science Translational MedicineĀ 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 byĀ Sanofi Genzyme, is a well-known inhibitor of a mitochondrial enzyme called dihydroorotate dehydrogenase (DHODH), that is crucial for the activity of T-cells.Ā However, how Aubagio selectively targets the autoreactive T-cells is poorly understood. To shed light on this matter, an internationalĀ 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 ā the surface proteins that can recognize a particular antigen (a protein that can elicit an immune response) ā 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+Ā 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 ā called cytokines ā at the cell level, but their overall decrease probably was due to the reduction in T-cell numbers. In line with these findings, CD4+Ā T-cells that produced the cytokine interferon gamma were significantly reduced with Aubagio treatment, whereas CD4+Ā 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 fromĀ 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. āTherapeutic 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,ā the researchers concluded.
May 23, 2019 News by Ana Pena PhD Stress-induced Changes in Gut Bacteria May Increase Risk of Autoimmune Disorders, Mouse Study Suggests 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 ā…
May 23, 2019 News by Alberto Molano, PhD Early Safety Data from Phase 1 Study of Immunotherapy in Progressive MS Patients To Be Detailed at EAN Early, positive safety results from a Phase 1 trial testing a potential immunotherapy,Ā ATA188, in people with progressive multiple sclerosisĀ 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”…
May 22, 2019 News by Joana Carvalho, PhD Reactivation of Ancient Viruses May Be Involved in MS Inflammatory Response, Study Says 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…
May 7, 2019 News by Jose Marques Lopes, PhD #AANAM – Mayzent Lessens Inflammation at Brain Meninges, Prevents Migration of Lymphocytes to Reduce Demyelination, Mouse Study Suggests Treatment with Mayzent (siponomod) may reduce myelin deterioration by lessening the accumulation of immune cells in brain meninges, and preventing the migration of pro-inflammatory lymphocytes into the brain, according to a study in a mouse model of multiple sclerosis (MS). The research, āA Mouse Model of…
April 26, 2019 News by Alice MelĆ£o, MSc Active Form of Vitamin D Can Regulate Immune Responses in Diseases, Including MS, Study Shows An active form of vitamin D can modulate the activity of immune cells and prevent autoimmune reactions known to be involved in several human diseases such as multiple sclerosis (MS). A study with that finding, led by researchers from The University of EdinburghĀ in Scotland, reveals a new layer…
March 11, 2019 News by Jose Marques Lopes, PhD Tecfidera May Work to Lower Relapses by Inducing Epigenetic Changes in T-cells, Study Suggests TreatingĀ multiple sclerosis with Tecfidera induces specific genetic alterations that may reduce the levels of immune T-cells targeting the central nervous system, researchers report. Environmental stimuli may induce epigenetic changes in cells ā meaning not alterations in the genes themselves, but changes in gene expression (the process by which information in a gene is synthesized to create a working product, like a protein). Epigenetic changes may induce MS development, as these alterations can cause T-cells to attack the central nervous system. One type of epigenetic change is DNA demethylation, the removal of methyl chemical groups, in which molecules involved in metabolism (such as fumarate) interact with enzymes known as DNA demethylases. This process in key for T-cell activation, function and memory, suggesting that it could be an immunomodulatory target. Fumaric acid esters were shown to be effective in MS clinical trials, leading to the approval ofĀ Tecfidera (by Biogen) for people with relapsing-remitting forms of the disease.Ā However, their complete mechanism of action remains unclear. Aiming to address this gap, scientists at theĀ Advanced Science Research Center (ASRC) at The Graduate Center of The City University of New YorkĀ and theĀ Icahn School of Medicine at Mount Sinai, recruited 98 MS patients, either previously untreated (47 people, mean age of 38.4), treated with Tecfidera (35 people, mean age of 42.3), or treated with glatiramer acetate (16 patients, mean age of 43.4) ā marketed asĀ CopaxoneĀ byĀ Teva Pharmaceuticals, with generic forms byĀ SandozĀ (asĀ Glatopa) and byĀ Mylan. All patients had stable disease for at least three months, but disease duration was shortest in untreated patients ā 40.4 months vs. 130 months in those given Tecfidera, and 100 months in patients using glatiramer acetate. Blood samples were collected from each participant to assess epigenetic changes in T-cells expressing the cell surface marker CD4. MS patients typicallyĀ have an activated formĀ of these cells in their blood and cerebrospinal fluid, the liquid surrounding the brain and spinal cord. Results revealed that, compared to the other two groups,Ā treatmentĀ with Tecfidera was associated with a lower percentage of T-cells containing the CD3, CD4, and CD8 markers, as well as lower levels of subsets of T-cells expressing the CCR4 and CCR6 receptors, which are critical to T-cell migration to the gut, brain, and skin. Treatment with glatiramer acetate resulted in significantly milder alterations in T-cell percentages compared to no treatment. Researchers then found that FAEs induce excessive methylation ā the addition of methyl groups ā in T-cells containing CD4, compared to glatiramer acetate. Specifically, this overmethylation was observed in a micro-RNA ā tiny RNA molecules than control gene expression ā known as miR-21, key for the differentiation of a subset of T-cells called T helper-17 (Th17) cells and for CCR6 expression in MS mouse models. These Th17 cells are critical in tissue inflammation and destruction, and have beenĀ implicatedĀ in MS. The epigenetic effects of FAEs were subsequently validated by comparing pre- to post-treatment with Tecfidera in seven patients. In turn, in vitroĀ (lab dish) experiments showed that FAEs act specifically on the activation of naĆÆve T-cells ā those able to respond to new pathogens to the immune system ā containing the CD4 or the CD8 markers. Of note, patients with MS have shown increased miR-21 levels, particularly during acute relapses. As such, the team hypothesized that its hypermethylation by FAEs could contribute to remission and the prevention of relapses in this patient population. These results "suggest that the metabolic-epigenetic interplay in T-cells could be harnessed for therapeutic purposes," the researchers wrote, and that the immunomodulatory effect of FAEs in MS is due at least in part to the epigenetic regulation of T-cells. The researchers believe that their findings have a broader implication, beyond MS. "Our findings about therapeutically active metabolites have implications for the treatment of not only multiple sclerosis but also other autoimmune diseases, such as psoriasis and inflammatory bowel disease, which involve the same type of T-cells," Achilles Ntranos, the studyās lead author, said in a press release. "Understanding the epigenetic effect of metabolites on the immune system will help us develop several novel strategies for the treatment of autoimmune diseases, which could help patients and physicians achieve better clinical outcomes," Ntranos added. Patrizia Casaccia, the studyās senior author, concluded:Ā "It may one day be possible to target and suppress production of the specific brain-homing T-cells that play a role in the development of MS."