February 18, 2019 News by Jonathan Grinstein Protein That Turns Certain T-cells into Inflammatory Agents Identified in Early Study A protein called Satb1 appears to be the "on switch" that turns a type of T-cell called Th17 from its typical protective role into one that is disease-causing, and key in the development of multiple sclerosis (MS) and other inflammatory autoimmune disorders, a study reports. These findingsĀ suggest thatĀ Satb1 may be a therapeutic target for autoimmune diseases like MS. The research article, āSatb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation,ā was published in the journalĀ Nature Communications. Immune cells called T-helper 17 (Th17) cells play a range of roles in immunity, including protecting against infecting pathogens ā bacteria, viruses, and other microorganisms that can cause disease. But Th17 cells are also players in the development of such autoimmune diseases as MS, psoriasis, inflammatory bowel disease, and rheumatoid arthritis. This is because Th17 cells can be stimulated to become T-cells that engage in pathogenic, or disease-causing, immune programs. How Th17 cells switch from their typical and helpful immunity role to that of a pathogenic actor has not been resolved, although it is thought critical to treating inflammatory autoimmune diseases. An international team led by researchers at Osaka University and Kyoto University, in Japan, tried to identify the mechanism behind the disease-causing program of Th17 cells. To do so, they built upon previous findings showing that a protein regulator called Satb1 is important in the development of Th17 cell subsets. "We have known for some time that Satb1 is indispensable for the development of T-cells in the thymus. However, how it is involved in the regulation of pathogenic processes of Th17 cells in inflamed tissues had not been examined," Keiko Yasuda, MD, the study'sĀ lead author, said in a press release. Researchers used a standard mouse model of MS, called experimental autoimmune encephalomyelitis (EAE) mice. These animals had genetically-modified Th17 cells that lacked Satb1. Researchers tested how Th17 cells lacking Satb1 acted when subject to inflammatory conditions, and how they were stimulated to activate a "pathogenic effector program." Interestingly, these modified mice were resistant to the development of EAE, or MS-like, disease. Researchers saw fewer Th17 cells infiltrating the animals' spinal cord. Also, Th17 cells lacking Satb1 showed poorer production of key pathogenic signaling molecules in autoimmunity, notably one called granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is known to cause localized tissue inflammation in MS and other inflammatory autoimmune diseases. Researchers went on to show that Satb1 can act as a switch between benign and pathogenic Th17 cells, depending on their exposure to healthy or inflammatory conditions. They found molecules that boost the pathogenicity of Th17 cells, such as Bhlhe40, and molecules that promote normal immune function, such as PD-1. Ā Of note, PD-1 is shut down when Th17 cells engage in their pathogenic effector program. These results showed Satb1 to be a key regulator of Th17 cell pathogenicity in these MS mice. Halting Th17 cells from making Satb1 may offer a way of treatting various autoimmune diseases. āTogether, our findings, in addition to providing novel insights into the molecular mechanisms underlying the pathogenic program of tissue Th17 cells in mice, may help design novel immunotherapeutic approaches such as small molecule modifiers of Satb1 for the treatment of autoimmune diseases,ā the researchers wrote. Future studies are needed to confirm these results in people. A previous study in people also suggested a link between Satb1 and the pathogenic function of Th17 cells in the central nervous system of MS patients. Overall, "our results suggest that manipulating Satb1 gene expression in Th17 cells could form the basis of novel treatments for various autoimmune diseases caused by Th17 cells. If we can prevent the pathogenic processes of Th17 cells, we may be able to alleviate or even eliminate disease symptoms," concluded Shimon Sakaguchi, PhD, one of the study's senior authors.
January 15, 2019 News by Jose Marques Lopes, PhD Ocrevus Targets Certain T-Cells, Along with B-Cells, in MS Patients, Study Reports 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, āOcrelizumab Depletes CD20+Ā T Cells in Multiple Sclerosis Patients,ā was published in the journal Cells. AutoreactiveĀ immune T-cells, which attack the bodyās 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 isĀ Genentechās 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 ā the liquid surrounding the brain and spinal cord ā and chronic brain lesions of MS patients, and show an elevated expression of the CD8 and CD45 markers. Off-label use of rituximabĀ (marketed as Rituxan in the U.S. and MabThera in Europe), a lymphoma and rheumatoid arthritis treatmentĀ 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 rituximabās 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 SchoolĀ 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 patientsā 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 forĀ 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 ā white blood cells that include T- and B-cells ā and for a significant proportion (18.4%) of all CD20 cells. Evaluation of the cellsā 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. āOur 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,ā the researchers wrote. āThese 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,ā they added. However, they also emphasized that the findings need to be confirmed in studies with larger groups of MS patients.
January 3, 2019 News by Jose Marques Lopes, PhD Stem-like Th17 Cells May Lead to New Therapeutic Approaches for MS, Other Autoimmune Diseases, Study Suggests 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.
December 21, 2018 News by Patricia Inacio, PhD Stem Cell Transplant Lessens Disability and Relapses in RRMS Patients, Phase 2 Trial Shows Treatment withĀ autologous hematopoietic stem cell transplantĀ (aHSCT) led to a sustained decrease in disability and almost no clinical relapses in patients withĀ relapsing-remitting multiple sclerosisĀ (RRMS)Ā who had failed to respond to prior immunosuppressive therapies, an Australian Phase 2 trial shows. Trial findings were published in the study, āProspective phase…
December 5, 2018 News by Patricia Inacio, PhD Aspirin Suppresses MS Symptoms by Preventing Loss of Regulatory T-cells, Mouse Study Shows Aspirin, administered orally at low doses, was sufficient to suppress multiple sclerosis (MS) symptoms in a mouse model of relapsing-remitting MS (RRMS) and chronic MS, a study reports. The clinical benefits of aspirin were linked to an increase in the number of regulatory T-cells, those responsible for shutting…
November 27, 2018 News by Ana Pena PhD Homotaurine Compound May Be New Class of Treatment for MS, Mouse Study Suggests Homotaurine, a compound proven safe for humans in long-term clinical trials, has eased autoimmune responses, brain inflammation, and multiple sclerosis-like symptoms in a mouse model of the disease, a study has found. The findings represent proof-of-principle evidence that homotaurine may represent a new potential class…
November 21, 2018 News by Patricia Inacio, PhD Phase 1 Trial of ATA190 Cell Therapy Shows Promise in Treating Progressive MS Atara Biotherapeuticsā investigational ATA190, a cell therapy that wipes out immune B-cells infected with the Epstein-Barr virus (EBV), led to neurological improvements and reduced symptoms in patients with primary and secondary progressive multiple sclerosis (MS), a Phase 1 trial shows. The trial results were published in the Journal…
November 2, 2018 News by Jose Marques Lopes, PhD Study Sheds New Light on Tecfidera’s Inhibitory Mechanism of Action 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…
October 29, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: Cannabis Pill, Stem Cells in Outer Space, Gut Bacteria and T-cells, Herpes and MS Stanford Researchers Open Medical Cannabis Company with Oral Therapy for MS Pain, Spasticity as Initial Goal Let’s be clear up front. There’s no indication that you’ll be able to buy a cannabis pill from this company anytime soon ā or ever. The company’s website says that testing…
October 26, 2018 News by Patricia Inacio, PhD Infection with Common Herpes Virus Speeds MS-like Disease Onset and Progression in Primate Model, Study Reports Infection with theĀ most common member of the herpes virus family, called HHV-6, may pass unnoticed and without symptoms, but the very act of being infected significantly accelerated the development and progression of aĀ multiple sclerosis-like disease in nonhuman primates, a study reports. Its findings support the role of viral infection in…
October 19, 2018 News by Alice MelĆ£o, MSc Enzyme Produced by Gut Bacteria Linked to T-cell Attacks on Myelin in Study An enzyme produced by bacteria in the gut was seen to activate immune cells linked to the development and progression ofĀ multiple sclerosis, a finding that mayĀ pave the way for a vaccine that might alter autoimmune mechanisms involved in MS. The study, ā…
October 12, 2018 News by BioNews Staff #ECTRIMS2018 – From Sun to Salt: Growing Role of Environment in MS A person’s genes influence the development of multiple sclerosis (MS), but so does the environment ā both that in which an MS patient lives, and that which a patient creates through diet and other lifestyle choices, researchers said in a Thursday session at the 34th congress of the European…
October 10, 2018 News by Jose Marques Lopes, PhD #ECTRIMS2018 ā Vitamin D May Boost Glucocorticosteroid Effectiveness in MS Relapses, Study Suggests Vitamin D may increase the therapeutic benefits of glucocorticosteroids (GCs) forĀ multiple sclerosis (MS) through a protein complex called mTORc1, according to a study in a mouse model and in cells from MS patients. The study, āVitamin D augments glucocorticosteroid efficacy via inhibition of mTORc1,ā was presented…
September 20, 2018 News by Vijaya Iyer, PhD Rapamycin, Approved for Other Indications, Potentially Effective for MS, Study Suggests Treatment with Rapacan (rapamycin) decreased the size and volume of brain lesions in patients with multiple sclerosis (MS), an Iranian study reports. The study, āPromising effect of rapamycin on multiple sclerosis,ā was published in the journal Multiple Sclerosis and Related Disorders. Rapamycin, or sirolimus, is an immunosuppressive…
September 20, 2018 News by Patricia Inacio, PhD Lymphatic Vessels of Brain Carry Messages That Appear to Promote MS, Study Reports Lymphatic vessels, the āroadsā that work to clear waste material from the brain, can also carry messages that direct immune system attacks against myelin, promoting the onset of multiple sclerosis (MS), new study shows. While the identity of these messages remains unknown, the findings suggest that blocking these signals could…
September 10, 2018 Columns by Ed Tobias MS News that Caught My Eye Last Week: B- and T-cells, Tysabri, Sexual Silence How B-cells Work to Promote T-cell Attacks on Myelin That Lead to MS Detailed in Study I keep a close eye on reports about B-cells and T-cells because they’re the targets of Lemtrada, which is my current disease-modifying therapy. (The DMT Ocrevus targets B-cells alone). So, this…
September 7, 2018 News by Ana Pena PhD How B-cells Work to Promote T-cell Attacks on Myelin That Lead to MS Detailed in Study B-cells in the immune system play an important role in the unfolding of inflammation and brain lesions in multiple sclerosis (MS), largely by how they influence the actions of another immune system cell, called T-cells, a new study reports. Its findings help explain why therapies…
August 6, 2018 News by Jose Marques Lopes, PhD Loss of Specific microRNA Seen to Lessen Disease Severity and Myelin Loss in MS Mouse Model Removing a specific microRNA molecule ā miR-150 ā eased disease severity, inflammation, and loss of myelin in a mouse model of multiple sclerosis (MS), researchers report. Their study, āSilencing miR-150 Ameliorates Experimental Autoimmune Encephalomyelitis,ā was published in the journal Frontiers in Neuroscience. Micro RNAs (miRNAs) are…
July 16, 2018 Columns by Ed Tobias MS News That Caught My Eye Last Week: Fasting Study, ‘Bad’ T-cells, Brain Volume, Ocrevus in Scotland Missouri Trial to Examine if Fasting Alters Gut Microbiome and Immune System of RRMS Patients in Helpful Ways The impact of various diets on multiple sclerosis (MS) has been studied, but this new study will look into whether fasting has an impact. The researchers at Washington University…
July 12, 2018 News by Patricia Inacio, PhD Overreactive T-cells Can Transition into T-cells That Control the Immune Response, Study Shows New research shows that overreactive and tissue-damaging T-cells can transition into regulatory T-cells that help to control the immune system’s response. These findings open the door to further understanding of the mechanism underlying this transition, knowledge that can help scientists in designing more effective, targeted immunotherapies for diseases like multiple…
June 27, 2018 News by Patricia Inacio, PhD New Fluorescent Imaging Tool Allows Researchers to Track Immune Cell Dynamics in MS Mouse Model A new fluorescent imaging strategy allows researchers to track T-cells and further understand their dynamics in vivo, giving them insight into what happens when these immune cells attack myelin in a mouse model of multiple sclerosis (MS). The new technology was reported in the study, āA timer for…
May 17, 2018 News by Patricia Inacio, PhD Viral Infection Promotes Factor in T-cells Leading to Brain Tissue Destruction Infection with lymphocytic choriomeningitis virus triggers expression of a factor called TOX in immune cells strengthening their migration into the brain and promoting damaging effects, including inflammation and tissue destruction. These findings represent a new piece of the puzzle about the mechanism underlying autoimmune diseases Ā like multiple sclerosis (MS).
May 4, 2018 News by Jose Marques Lopes, PhD Fracking Chemicals May Lead to Earlier Onset, More Severe MS, Mouse Study Suggests Exposure to fracking chemicals during pregnancy may aggravate multiple sclerosis (MS) severity and induce an earlier start of symptoms, a new study in mice suggests. The study, āDevelopmental Exposure to a Mixture of 23 Chemicals Associated With Unconventional Oil and Gas Operations Alters the Immune System…
April 18, 2018 News by Patricia Inacio, PhD #AAN2018 – Ocrevus Decreases Biomarkers of MS Patients’ Nerve Cell Damage, Phase 3 Trial Shows Genentech’sĀ Ocrevus (ocrelizumab)Ā reduces levels of cerebrospinal fluid biomarkers that denote nerve cell damage in multiple sclerosis patients, a Phase 3 clinical trial shows. Researchers will present the results at theĀ American Academy of Neurology’s annual meetingĀ in Los Angeles, April 21-27. The presentation will be titled āInterim Analysis of the…
March 13, 2018 News by Jose Marques Lopes, PhD High Levels of Protein Can Disrupt Blood-Brain Barrier in MS, Study Finds High levels of a protein called calnexin in the brain may disrupt the blood-brain barrier of patients with multiple sclerosis, a Canadian study suggests. The finding could lead to new treatment strategies to prevent brain damage in MS. The research, āCalnexin is necessary for T cell…
January 10, 2018 News by Jose Marques Lopes, PhD Stem Cell Combo Therapy Shows Efficacy in MS Mouse Model, Korean Study Shows A combination therapy of low-dose methylprednisolone and interferon (IFN)-beta-secreting stem cells is effective in a mouse model of multiple sclerosis (MS), a new Korean study suggests. The research, āEffective combination of methylprednisolone and interferon Ī²-secreting mesenchymal stem cells in a model of multiple sclerosis,ā appeared in the…
December 18, 2017 News by Patricia Silva, PhD Cell Recycling Process Helps Trigger Immune Attack on Protective Nerve Cell Protein Myelin A cell recycling process helps trigger an immune response against myelin, the protective layer covering nerve cell axons to aid in signal transmission, a multiple sclerosis (MS) study indicates. WhenĀ University of ZurichĀ researchers eliminated the process, mice developed much milder forms of an MS-like disease. Loss of myelin is the…
November 22, 2017 News by Alice MelĆ£o, MSc Gut Bacteria Contribute to MS Onset and Development, Rutgers Mouse Study Shows Exposure to certain gut bacteria at a young age may cause multiple sclerosis (MS) and fuel its progression, a new mouse study shows. The study, āGut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood,ā appeared in the journal Proceedings of the National…
November 6, 2017 Columns by Ed Tobias MS News That Caught My Eye Last Week: Older Patients, Stem Cells, Myelin, B-cells vs. T-cells #MSParis2017 ā Trial to See if Disease-modifying Therapies Not Necessary in Older MS Patients This tops my list this week because, at age 69, I certainly fit the definition of an “older” MS patient. The study is hoping to enroll 300 MS patients in the U.S. who…
October 31, 2017 News by Patricia Silva, PhD #MSParis2017 – T-cell vs. B-cell Debate More Meeting of Minds Than ‘Rumble in the Jungle’ News commentary One particular session on Day 2 of the four-day 7th Joint ECTRIMS-ACTRIMS Meeting ā which drew 10,000 researchers, doctors, industry representatives, and patient advocates to hear about advances in multiple sclerosis (MS) treatment and understanding ā attracted so much interest that all seats were taken in the…