Multiple sclerosis New Drugs Review
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Invitation and call for Qualified Curators in Multiple sclerosis

Invitation and call for Qualified Curators in Multiple sclerosis | Multiple sclerosis New Drugs Review | Scoop.it

What started as a review of one the experimental drug in MS in 2007 at another platform and then migration to this site in 2011 has now become a collection on the topic. 

 

Followers and readers from universities, research institutes, pharmaceutical and biotech industry and regulators are invited to join as curators. We can have upto 5 curators on each topic. If interested leave a comment with your background and experience.

 

Comments section is now open for interested curators.

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Disseminated Histoplasmosis in a Patient With Multiple Sclerosis Treated With Fingolimod | Neurology Neuroimmunology & Neuroinflammation

Disseminated Histoplasmosis in a Patient With Multiple Sclerosis Treated With Fingolimod | Neurology Neuroimmunology & Neuroinflammation | Multiple sclerosis New Drugs Review | Scoop.it
Treatment for disseminated histoplasmosis should be initiated promptly because the disease is almost entirely fatal within 3 months.1 Liposomal amphotericin B is recommended as first-line therapy in those with severe disease with a transition to intraconazole after 1–2 weeks of amphotericin to complete 12 months of therapy.7 For immunocompromised patients, lifelong suppressive antifungal therapy may be required if immunosuppression is expected to persist.7

This case highlights the importance of considering histoplasmosis in patients with MS on immunomodulatory therapy and exposure risk factors because gastrointestinal histoplasmosis can mimic malignancy in the absence of pulmonary disease. Prompt diagnosis and early treatment are vital because disseminated histoplasmosis is ultimately fatal without treatment.
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Efficacy of probiotics in multiple sclerosis: a systematic review of preclinical trials and meta-analysis of randomized controlled trials - Food & Function (RSC Publishing)

Efficacy of probiotics in multiple sclerosis: a systematic review of preclinical trials and meta-analysis of randomized controlled trials - Food & Function (RSC Publishing) | Multiple sclerosis New Drugs Review | Scoop.it
Preliminary evidence shows the potential role of probiotics in ameliorating multiple sclerosis (MS); however, the effects of probiotics on MS remain unclear.Therefore, the aim of this study was to evaluate the efficacy of probiotics on multiple sclerosis by systematically reviewing the preclinical...
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Limited Utility of Gadolinium Contrast Administration in Routine Multiple Sclerosis Surveillance - Johnston - 2021 - Journal of Neuroimaging

Limited Utility of Gadolinium Contrast Administration in Routine Multiple Sclerosis Surveillance - Johnston - 2021 - Journal of Neuroimaging | Multiple sclerosis New Drugs Review | Scoop.it
ABSTRACT BACKGROUND AND PURPOSE Assess the incidence of enhancing lesions on follow‐up MRIs in patients with multiple sclerosis (MS) to determine the utility of intravenous, gadolinium‐based contra...
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Developing a clinical pathway to identify and manage cognitive problems in Multiple Sclerosis: Qualitative findings from patients, family members, charity volunteers, clinicians and healthcare comm...

Developing a clinical pathway to identify and manage cognitive problems in Multiple Sclerosis: Qualitative findings from patients, family members, charity volunteers, clinicians and healthcare comm... | Multiple sclerosis New Drugs Review | Scoop.it
Cognitive problems affect up to 70% of people with MS (pwMS) [1] and can negatively
impact quality of life and vocational activities [2-4]. Consequently, routine screening and management for cognitive problems in MS has been internationally recommended [5, 6], with addressing cognitive problems a...
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Long-term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis | Neurology

Long-term Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Multiple Sclerosis | Neurology | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
Objective To determine whether autologous hematopoietic stem cell transplantation (aHSCT) is able to induce durable disease remission in people with multiple sclerosis (MS), we analyzed the long-term outcomes after transplantation in a large cohort of patients with MS.

Methods To be included, a minimum dataset (consisting of age, MS phenotype, Expanded Disability Status Scale [EDSS] score at baseline, information on transplantation technology, and at least 1 follow-up visit after transplantation) was required.

Results Two hundred ten patients were included (relapsing-remitting [RR] MS 122 [58%]). Median baseline EDSS score was 6 (1–9); mean follow-up was 6.2 (±5.0) years. Among patients with RRMS, disability worsening–free survival (95% confidence interval [CI]) was 85.5% (76.9%–94.1%) at 5 years and 71.3% (57.8%–84.8%) at 10 years. In patients with progressive MS, disability worsening–free survival was 71.0% (59.4%–82.6%) and 57.2% (41.8%–72.7%) at 5 and 10 years, respectively. In patients with RRMS, EDSS significantly reduced after aHSCT (p = 0.001; mean EDSS change per year −0.09 [95% CI −0.15% to −0.04%]). In patients with RRMS, the use of the BCNU+Etoposide+Ara-C+Melphalan (BEAM) + anti-thymocyte globulin (ATG) conditioning protocol was independently associated with a reduced risk of no evidence of disease activity 3 failure (hazard ratio 0.27 [95% CI 0.14–0.50], p < 0.001). Three patients died within 100 days from aHSCT (1.4%); no deaths occurred in patients transplanted after 2007.

Conclusions aHSCT prevents disability worsening in the majority of patients and induces durable improvement in disability in patients with RRMS. The BEAM + ATG conditioning protocol is associated with a more pronounced suppression of clinical relapses and MRI inflammatory activity.

Classification of Evidence This study provides Class IV evidence that for people with MS, aHSCT induces durable disease remission in most patients.
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Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis | PNAS

Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis | PNAS | Multiple sclerosis New Drugs Review | Scoop.it
RESEARCH ARTICLE Astrocytes lure CXCR2-expressing CD4+ T cells to gray matter via TAK1-mediated chemokine production in a mouse model of multiple sclerosis View ORCID ProfileYee Ming Khaw, View ORCID ProfileAbbey Tierney, Claire Cunningham, Katiria Soto-Díaz, Eunjoo Kang, View ORCID ProfileAndrew J. Steelman, and View ORCID ProfileMakoto Inoue PNAS February 23, 2021 118 (8) e2017213118; https://doi.org/10.1073/pnas.2017213118 Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved January 13, 2021 (received for review August 14, 2020) Article Figures & SI Info & Metrics PDF Significance Multiple sclerosis (MS) is a chronic neurological disease characterized by demyelination and neuronal damage. While T cells are consistently detected in the gray matter of human MS samples, they are rarely seen in the gray matter of the most common mouse model of MS. Here, we show a modified mouse model that is characterized by a high degree of neuronal damage, T cell infiltration, and reactive gliosis in spinal cord gray matter. Using conditional knockout mice, we show that T cell migration to spinal cord gray matter depends on T cell expression of CXCR2 and astrocyte expression of TAK1-mediated chemokines such as CXCL1. Abstract Multiple sclerosis (MS) is a chronic neurological disease of the central nervous system driven by peripheral immune cell infiltration and glial activation. The pathological hallmark of MS is demyelination, and mounting evidence suggests neuronal damage in gray matter is a major contributor to disease irreversibility. While T cells are found in both gray and white matter of MS tissue, they are typically confined to the white matter of the most commonly used mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Here, we used a modified EAE mouse model (Type-B EAE) that displays severe neuronal damage to investigate the interplay between peripheral immune cells and glial cells in the event of neuronal damage. We show that CD4+ T cells migrate to the spinal cord gray matter, preferentially to ventral horns. Compared to CD4+ T cells in white matter, gray matter-infiltrated CD4+ T cells were mostly immobilized and interacted with neurons, which are behaviors associated with detrimental effects to normal neuronal function. T cell-specific deletion of CXCR2 significantly decreased CD4+ T cell infiltration into gray matter in Type-B EAE mice. Further, astrocyte-targeted deletion of TAK1 inhibited production of CXCR2 ligands such as CXCL1 in gray matter, successfully prevented T cell migration into spinal cord gray matter, and averted neuronal damage and motor dysfunction in Type-B EAE mice. This study identifies astrocyte chemokine production as a requisite for the invasion of CD4+T cell into the gray matter to induce neuronal damage. Footnotes ↵1To whom correspondence may be addressed. Email: makotoi{at}illinois.edu. Author contributions: Y.M.K. and M.I. designed research; Y.M.K., A.T., C.C., E.K., and M.I. performed research; K.S.-D. and A.J.S. contributed new reagents/analytic tools; Y.M.K., A.T., C.C., and E.K. analyzed data; and Y.M.K. and M.I. wrote the paper. The authors declare no competing interest. This article is a PNAS Direct Submission. This article contains supporting information online at https://www.pnas.org/lookup/suppl/doi:10.1073/pnas.2017213118/-/DCSupplemental. Data Availability All study data are included in the article and/or supporting information. Published under the PNAS license. View Full Text References ↵ L. Jasse et al., Persistent visual impairment in multiple sclerosis: Prevalence, mechanisms and resulting disability. Mult. Scler. 19, 1618–1626 (2013).OpenUrlCrossRefPubMed ↵ O. Hadjimichael, R. D. Kerns, M. A. Rizzo, G. Cutter, T. Vollmer, Persistent pain and uncomfortable sensations in persons with multiple sclerosis. Pain 127, 35–41 (2007).OpenUrlCrossRefPubMed ↵ T. J. Braley, R. D. Chervin, Fatigue in multiple sclerosis: Mechanisms, evaluation, and treatment. Sleep 33, 1061–1067 (2010).OpenUrlPubMed ↵ A. Souza et al., Multiple sclerosis and mobility-related assistive technology: Systematic review of literature. J. Rehabil. Res. Dev. 47, 213–223 (2010).OpenUrlCrossRefPubMed ↵ R. A. Rudick, Disease-modifying drugs for relapsing-remitting multiple sclerosis and future directions for multiple sclerosis therapeutics. Arch. Neurol. 56, 1079–1084 (1999).OpenUrlCrossRefPubMed ↵ S. Migliore et al., Validity of the minimal assessment of cognitive function in multiple sclerosis (MACFIMS) in the Italian population. Neurol. Sci. 37, 1261–1270 (2016).OpenUrl ↵ L. A. Rolak, Multiple sclerosis: It’s not the disease you thought it was. Clin. Med. Res. 1, 57–60 (2003).OpenUrlFREE Full Text ↵ C. Lucchinetti et al., Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Ann. Neurol. 47, 707–717 (2000).OpenUrlCrossRefPubMed ↵ C. F. Lucchinetti et al., Inflammatory cortical demyelination in early multiple sclerosis. N. Engl. J. Med. 365, 2188–2197 (2011).OpenUrlCrossRefPubMed ↵ B. D. Trapp et al., Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: A retrospective study. Lancet Neurol. 17, 870–884 (2018).OpenUrlCrossRefPubMed ↵ M. van der Poel et al., Transcriptional profiling of human microglia reveals grey-white matter heterogeneity and multiple sclerosis-associated changes. Nat. Commun. 10, 1139 (2019).OpenUrlCrossRefPubMed ↵ P. Ganter, C. Prince, M. M. Esiri, Spinal cord axonal loss in multiple sclerosis: A post-mortem study. Neuropathol. Appl. Neurobiol. 25, 459–467 (1999).OpenUrlCrossRefPubMed ↵ J. E. Holley, D. Gveric, J. Newcombe, M. L. Cuzner, N. J. Gutowski, Astrocyte characterization in the multiple sclerosis glial scar. Neuropathol. Appl. Neurobiol. 29, 434–444 (2003).OpenUrlCrossRefPubMed ↵ C. Bjartmar, J. R. Wujek, B. D. Trapp, Axonal loss in the pathology of MS: Consequences for understanding the progressive phase of the disease. J. Neurol. Sci. 206, 165–171 (2003).OpenUrlCrossRefPubMed ↵ M. Absinta et al., Association of chronic active multiple sclerosis lesions with disability in vivo. JAMA Neurol. 76, 1474–1483 (2019).OpenUrl ↵ J. C. Bot et al., The spinal cord in multiple sclerosis: Relationship of high-spatial-resolution quantitative MR imaging findings to histopathologic results. Radiology 233, 531–540 (2004).OpenUrlCrossRefPubMed ↵ M. Inglese, N. Oesingmann, P. Casaccia, L. Fleysher, Progressive multiple sclerosis and gray matter pathology: An MRI perspective. Mt. Sinai J. Med. 78, 258–267 (2011).OpenUrlCrossRefPubMed ↵ F. Agosta, E. Pagani, D. Caputo, M. Filippi, Associations between cervical cord gray matter damage and disability in patients with multiple sclerosis. Arch. Neurol. 64, 1302–1305 (2007).OpenUrlCrossRefPubMed ↵ B. F. Popescu, C. F. Lucchinetti, Meningeal and cortical grey matter pathology in multiple sclerosis. BMC Neurol. 12, 11 (2012).OpenUrlCrossRefPubMed ↵ J. T. Mony, R. Khorooshi, T. Owens, Chemokine receptor expression by inflammatory T cells in EAE. Front. Cell. Neurosci. 8, 187 (2014).OpenUrl ↵ R. F. Whittaker Hawkins et al., ICAM1+ neutrophils promote chronic inflammation via ASPRV1 in B cell-dependent autoimmune encephalomyelitis. JCI Insight 2, e96882 (2017).OpenUrl ↵ T. Derfuss et al., Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc. Natl. Acad. Sci. U.S.A. 106, 8302–8307 (2009). ↵ S. E. Lutz et al., Caveolin1 is required for Th1 cell infiltration, but not tight junction remodeling, at the blood-brain barrier in autoimmune neuroinflammation. Cell Rep. 21, 2104–2117 (2017).OpenUrlCrossRefPubMed ↵ B. Engelhardt, Molecular mechanisms involved in T cell migration across the blood-brain barrier. J. Neural Transm. (Vienna) 113, 477–485 (2006).OpenUrl ↵ Y. Takeshita, R. M. Ransohoff, Inflammatory cell trafficking across the blood-brain barrier: Chemokine regulation and in vitro models. Immunol. Rev. 248, 228–239 (2012).OpenUrlCrossRefPubMed ↵ A. A. Babcock, W. A. Kuziel, S. Rivest, T. Owens, Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS. J. Neurosci. 23, 7922–7930 (2003). ↵ B. Shrestha, S. Ge, J. S. Pachter, Resolution of central nervous system astrocytic and endothelial sources of CCL2 gene expression during evolving neuroinflammation. Fluids Barriers CNS 11, 6 (2014).OpenUrl ↵ H. C. Lu et al., STAT3 signaling in myeloid cells promotes pathogenic myelin-specific T cell differentiation and autoimmune demyelination. Proc. Natl. Acad. Sci. U.S.A. 117, 5430–5441 (2020). ↵ M. Inoue et al., An interferon-β-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage. Nat. Neurosci. 19, 1599–1609 (2016).OpenUrlCrossRefPubMed ↵ S. S. Yan et al., Suppression of experimental autoimmune encephalomyelitis by selective blockade of encephalitogenic T-cell infiltration of the central nervous system. Nat. Med. 9, 287–293 (2003).OpenUrlCrossRefPubMed ↵ J. R. Lees, P. T. Golumbek, J. Sim, D. Dorsey, J. H. Russell, Regional CNS responses to IFN-gamma determine lesion localization patterns during EAE pathogenesis. J. Exp. Med. 205, 2633–2642 (2008). ↵ M. Sivaguru, Y. M. Khaw, M. Inoue, A confocal reflection super-resolution technique to image golgi-cox stained neurons. J. Microsc. 275, 115–130 (2019).OpenUrl ↵ J. W. Hammond et al., Complement-dependent synapse loss and microgliosis in a mouse model of multiple sclerosis. Brain Behav. Immun. 87, 739–750 (2020).OpenUrl ↵ S. Rossi et al., Exercise attenuates the clinical, synaptic and dendritic abnormalities of experimental autoimmune encephalomyelitis. Neurobiol. Dis. 36, 51–59 (2009).OpenUrlCrossRefPubMed ↵ V. Siffrin et al., In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity 33, 424–436 (2010).OpenUrlCrossRefPubMed ↵ C. Q. Chu, S. Wittmer, D. K. Dalton, Failure to suppress the expansion of the activated CD4 T cell population in interferon gamma-deficient mice leads to exacerbation of experimental autoimmune encephalomyelitis. J. Exp. Med. 192, 123–128 (2000). ↵ K. R. Garrod et al., Dissecting T cell contraction in vivo using a genetically encoded reporter of apoptosis. Cell Rep. 2, 1438–1447 (2012).OpenUrlCrossRefPubMed ↵ Y. M. Khaw, C. Cunningham, A. Tierney, M. Sivaguru, M. Inoue, Neutrophil-selective deletion of Cxcr2 protects against CNS neurodegeneration in a mouse model of multiple sclerosis. J. Neuroinflammation 17, 49 (2020).OpenUrl ↵ M. V. Sofroniew, H. V. Vinters, Astrocytes: Biology and pathology. Acta Neuropathol. 119, 7–35 (2010).OpenUrlCrossRefPubMed ↵ B. M. Davis, M. Salinas-Navarro, M. F. Cordeiro, L. Moons, L. De Groef, Characterizing microglia activation: A spatial statistics approach to maximize information extraction. Sci. Rep. 7, 1576 (2017).OpenUrlCrossRefPubMed ↵ K. Soto-Díaz, M. B. Juda, S. Blackmore, C. Walsh, A. J. Steelman, TAK1 inhibition in mouse astrocyte cultures ameliorates cytokine-induced chemokine production and neutrophil migration. J. Neurochem. 152, 697–709 (2020).OpenUrl ↵ Z. Kang et al., Astrocyte-restricted ablation of interleukin-17-induced Act1-mediated signaling ameliorates autoimmune encephalomyelitis. Immunity 32, 414–425 (2010).OpenUrlCrossRefPubMed ↵ W. Cai et al., Insulin regulates astrocyte gliotransmission and modulates behavior. J. Clin. Invest. 128, 2914–2926 (2018).OpenUrlCrossRef ↵ F. Haroon et al., Gp130-dependent astrocytic survival is critical for the control of autoimmune central nervous system inflammation. J. Immunol. 186, 6521–6531 (2011). ↵ K. N. Gibson-Corley et al., A method for histopathological study of the multifocal nature of spinal cord lesions in murine experimental autoimmune encephalomyelitis. PeerJ 4, e1600 (2016).OpenUrl ↵ Y. Mori et al., Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model. Int. Immunol. 26, 93–101 (2014).OpenUrlCrossRefPubMed ↵ S. Othy et al., Regulatory T cells suppress Th17 cell Ca2+ signaling in the spinal cord during murine autoimmune neuroinflammation. Proc. Natl. Acad. Sci. U.S.A. 117, 20088–20099 (2020). ↵ H. Pasantes-Morales, K. Tuz, Volume changes in neurons: Hyperexcitability and neuronal death. Contrib. Nephrol. 152, 221–240 (2006).OpenUrlPubMed ↵ D. J. Jun et al., Extracellular ATP mediates necrotic cell swelling in SN4741 dopaminergic neurons through P2X7 receptors. J. Biol. Chem. 282, 37350–37358 (2007). ↵ P. Freund et al., Disability, atrophy and cortical reorganization following spinal cord injury. Brain 134, 1610–1622 (2011).OpenUrlCrossRefPubMed ↵ R. Magliozzi et al., A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann. Neurol. 68, 477–493 (2010).OpenUrlCrossRefPubMed ↵ J. W. Peterson, L. Bö, S. Mörk, A. Chang, B. D. Trapp, Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann. Neurol. 50, 389–400 (2001).OpenUrlCrossRefPubMed ↵ T. Okuno et al., Roles of Sema4D-plexin-B1 interactions in the central nervous system for pathogenesis of experimental autoimmune encephalomyelitis. J. Immunol. 184, 1499–1506 (2010). ↵ S. Lively, L. C. Schlichter, Microglia responses to pro-inflammatory stimuli (LPS, IFNγ+TNFα) and reprogramming by resolving cytokines (IL-4, IL-10). Front. Cell. Neurosci. 12, 215 (2018).OpenUrl ↵ L. Walter, H. Neumann, Role of microglia in neuronal degeneration and regeneration. Semin. Immunopathol. 31, 513–525 (2009).OpenUrlCrossRefPubMed ↵ H. Lassmann, J. van Horssen, D. Mahad, Progressive multiple sclerosis: Pathology and pathogenesis. Nat. Rev. Neurol. 8, 647–656 (2012).OpenUrlCrossRefPubMed ↵ S. A. O’Sullivan, C. O’Sullivan, L. M. Healy, K. K. Dev, G. K. Sheridan, Sphingosine 1-phosphate receptors regulate TLR4-induced CXCL5 release from astrocytes and microglia. J. Neurochem. 144, 736–747 (2018).OpenUrlCrossRefPubMed ↵ F. Doetsch, I. Caillé, D. A. Lim, J. M. García-Verdugo, A. Alvarez-Buylla, Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97, 703–716 (1999).OpenUrlCrossRefPubMed ↵ C. Liu et al., The BAF45D protein is preferentially expressed in adult neurogenic zones and in neurons and may be required for retinoid acid induced PAX6 expression. Front. Neuroanat. 11, 94 (2017).OpenUrl ↵ T. Ishii et al., Endogenous reactive oxygen species cause astrocyte defects and neuronal dysfunctions in the hippocampus: A new model for aging brain. Aging Cell 16, 39–51 (2017).OpenUrlCrossRefPubMed ↵ K. J. Eash, A. M. Greenbaum, P. K. Gopalan, D. C. Link, CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J. Clin. Invest. 120, 2423–2431 (2010).OpenUrlCrossRefPubMed ↵ J. M. Rumble et al., Neutrophil-related factors as biomarkers in EAE and MS. J. Exp. Med. 212, 23–35 (2015). ↵ S. Blackmore et al., Influenza infection triggers disease in a genetic model of experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. U.S.A. 114, E6107–E6116 (2017). ↵ L. Jin, S. Batra, D. N. Douda, N. Palaniyar, S. Jeyaseelan, CXCL1 contributes to host defense in polymicrobial sepsis via modulating T cell and neutrophil functions. J. Immunol. 193, 3549–3558 (2014). ↵ M. Chini et al., Resolving and rescuing developmental miswiring in a mouse model of cognitive impairment. Neuron 105, 60–74.e7 (2020).OpenUrlCrossRefPubMed ↵ J. Y. Tinevez et al., TrackMate: An open and extensible platform for single-particle tracking. Methods 115, 80–90 (2017).OpenUrlCrossRefPubMed ↵ Y. Dombrowski et al., Regulatory T cells promote myelin regeneration in the central nervous system. Nat. Neurosci. 20, 674–680 (2017).OpenUrlCrossRefPubMed ↵ R. B. Tripathi, L. E. Rivers, K. M. Young, F. Jamen, W. D. Richardson, NG2 glia generate new oligodendrocytes but few astrocytes in a murine experimental autoimmune encephalomyelitis model of demyelinating disease. J. Neurosci. 30, 16383–16390 (2010). Log in using your username and password Username * Password * Log in Forgot your user name or password? Log in through your institution You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password. If your organization uses OpenAthens, you can log in using your OpenAthens username and password. To check if your institution is supported, please see this list. Contact your library for more details. Purchase access You may purchase access to this article. This will require you to create an account if you don't already have one. Subscribers, for more details, please visit our Subscriptions FAQ. Please click here to log into the PNAS submission website. Previous Next Share Sign up for the PNAS Highlights newsletter to get in-depth stories of science sent to your inbox twice a month: Sign up for Article Alerts Sign up ARTICLE CLASSIFICATIONS Biological SciencesImmunology and Inflammation JUMP TO SECTION YOU MAY ALSO BE INTERESTED IN Scientists should pursue a strategic approach to research, focusing on the accumulation of evidence via designed sequences of studies. Image credit: Dave Cutler (artist). Despite myriad challenges, clinicians see room for progress. Image credit: Shutterstock/David Tadevosian. Sneaky intracellular bacteria know when to defend themselves and multiply. Image credit: Camilla Ciolli Mattioli. Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018. Listen Past PodcastsSubscribe A study demonstrates how two enzymes—MHETase and PETase—work synergistically to depolymerize the plastic pollutant PET. Image credit: Aaron McGeehan (artist). Similar Articles
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Antigen-specific therapy for multiple sclerosis


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Multiple sclerosis (MS) develops owing to failed peripheral immune tolerance for a specific self-antigen (Ag). However, MS therapy based on restoration of such immune tolerance has been hampered by uncertainty regarding the relevant myelin Ags in patients with MS. Casella et al. developed a therapeutic approach using oligodendrocyte-derived extracellular vesicles (Ol-EVs), which naturally contain the most relevant myelin Ags. Intravenous injection of Ol-EVs suppressed clinical disease prophylactically and therapeutically in chronic and relapsing–remitting EAE mouse models. The effects of Ol-EVs were myelin Ag dependent and mediated by monocytes. Notably, in vitro, human oligodendrocytes released EVs containing myelin Ags.
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Oxidized phosphatidylcholines found in multiple sclerosis lesions mediate neurodegeneration and are neutralized by microglia

Oxidized phosphatidylcholines found in multiple sclerosis lesions mediate neurodegeneration and are neutralized by microglia | Multiple sclerosis New Drugs Review | Scoop.it
Abstract
Neurodegeneration occurring in multiple sclerosis (MS) contributes to the progression of disability. It is therefore important to identify and neutralize the mechanisms that promote neurodegeneration in MS. Here, we report that oxidized phosphatidylcholines (OxPCs) found in MS lesions, previously identified as end-product markers of oxidative stress, are potent drivers of neurodegeneration. Cultured neurons and oligodendrocytes were killed by OxPCs, and this was ameliorated by microglia. After OxPC injection, mouse spinal cords developed focal demyelinating lesions with prominent axonal loss. The depletion of microglia that accumulated in OxPC lesions exacerbated neurodegeneration. Single-cell RNA sequencing of lesioned spinal cords identified unique subsets of TREM2high mouse microglia responding to OxPC deposition. TREM2 was detected in human MS lesions, and TREM2−/− mice exhibited worsened OxPC lesions. These results identify OxPCs as potent neurotoxins and suggest that enhancing microglia-mediated OxPC clearance via TREM2 could help prevent neurodegeneration in MS.
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MicroRNA in multiple sclerosis - ScienceDirect

MicroRNA in multiple sclerosis - ScienceDirect | Multiple sclerosis New Drugs Review | Scoop.it
Highlights

MiRNAs are involved in the pathogenesis of multiple sclerosis (MS), mainly affecting glial cells and peripheral immune cells.


Circulating miRNAs are expected to become new biological diagnostic biomarkers for MS.


Dysregulated miRNA may be served as potential therapeutic application in multiple sclerosis.
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Exploring the Rationale, Results, and Real-World Clinical Potential of BTK Inhibitors in the Management of Multiple Sclerosis

Exploring the Rationale, Results, and Real-World Clinical Potential of BTK Inhibitors in the Management of Multiple Sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
In this educational activity, our experts offer insights into the rationale for developing BTK inhibitors to treat MS, current evidence regarding BTK inhibitors in the treatment of MS, and potential roles of BTK inhibitors for individualized MS management, based on available evidence and patient...
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The Effect of Cannabis on the Clinical and Cytokine Profiles in Patients with Multiple Sclerosis

The Effect of Cannabis on the Clinical and Cytokine Profiles in Patients with Multiple Sclerosis | Multiple sclerosis New Drugs Review | Scoop.it
<i>Background</i>. Multiple studies have reported that cannabis administration in multiple sclerosis patients is associated with decreased symptom severity. This study was conducted to evaluate the prevalence of cannabis abuse in multiple sclerosis cases and to evaluate the effect of cannabis on...
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Thalamic Nuclei Volumes and Their Relationships to Neuroperformance in Multiple Sclerosis: A Cross‐Sectional Structural MRI Study - Bergsland - 2021 - Journal of Magnetic Resonance Imaging

Thalamic Nuclei Volumes and Their Relationships to Neuroperformance in Multiple Sclerosis: A Cross‐Sectional Structural MRI Study - Bergsland - 2021 - Journal of Magnetic Resonance Imaging | Multiple sclerosis New Drugs Review | Scoop.it
Background Although reduced thalamic volume is associated with multiple sclerosis (MS)‐related clinical impairment, the role of individual thalamic nuclei remains poorly understood. Purpose/Hypothe...
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JCI Insight - A STAT3 inhibitor ameliorates CNS autoimmunity by restoring Teff:Treg balance

JCI Insight - A STAT3 inhibitor ameliorates CNS autoimmunity by restoring Teff:Treg balance | Multiple sclerosis New Drugs Review | Scoop.it
Reestablishing an appropriate balance between T effector cells (Teff) and Tregs is essential for correcting autoimmunity. Multiple sclerosis (MS) is an immune-mediated chronic CNS disease characterized by neuroinflammation, demyelination, and neuronal degeneration, in which the Teff:Treg balance is skewed toward pathogenic Teffs Th1 and Th17 cells. STAT3 is a key regulator of Teff:Treg balance. Using the structure-based design, we have developed a potentially novel small-molecule prodrug LLL12b that specifically inhibits STAT3 and suppresses Th17 differentiation and expansion. Moreover, LLL12b regulates the fate decision between Th17 and Tregs in an inflammatory environment, shifting Th17:Treg balance toward Tregs and favoring the resolution of inflammation. Therapeutic administration of LLL12b after disease onset significantly suppresses disease progression in adoptively transferred, chronic, and relapsing-remitting experimental autoimmune encephalomyelitis. Disease relapses were also significantly suppressed by LLL12b given during the remission phase. Additionally, LLL12b shifts Th17:Treg balance of CD4+ T cells from MS patients toward Tregs and increases Teff sensitivity to Treg-mediated suppression. These data suggest that selective inhibition of STAT3 by the small molecule LLL12b recalibrates the effector and regulatory arms of CD4+ T responses, representing a potentially clinically translatable therapeutic strategy for MS.
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Diagnosis and Treatment of Multiple Sclerosis—A Review | Demyelinating Disorders | JN Learning | AMA Ed Hub

Diagnosis and Treatment of Multiple Sclerosis—A Review | Demyelinating Disorders | JN Learning | AMA Ed Hub | Multiple sclerosis New Drugs Review | Scoop.it
Highly effective B-cell therapies like rituximab and ofatumumab have changed the outlook for patients with multiple sclerosis (MS).Alexander Rae-Grant, MD, emeritus professor of neurology at the Cleveland Clinic Lerner College of Medicine, discusses recent advances in the diagno...
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JCM | Assessment of Disability Progression Independent of Relapse and Brain MRI Activity in Patients with Multiple Sclerosis in Poland

JCM | Assessment of Disability Progression Independent of Relapse and Brain MRI Activity in Patients with Multiple Sclerosis in Poland | Multiple sclerosis New Drugs Review | Scoop.it
The aim of the study was to verify the association of clinical relapses and brain activity with disability progression in relapsing/remitting multiple sclerosis patients receiving disease-modifying treatments in Poland.
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Multiple sclerosis‐specific T‐cell receptors | Physician's Weekly

Multiple sclerosis‐specific T‐cell receptors | Physician's Weekly | Multiple sclerosis New Drugs Review | Scoop.it
Multiple sclerosis (MS) is an incendiary demyelinating issue in which both hereditary and ecological elements play significant pathogenic roles.1 Clinical highlights of MS vary by identity. For example, Japanese patients with MS have a milder illness course than patients in the United Kingdom2 and cerebellar hemispheric sores are less every now and again saw in Japanese patients than in Caucasian patients. Perhaps the most as of late created strategies is Grouping of Lymphocyte Interactions by Paratope Hotspots (GLIPH), which use arrangement likeness for bunching to foresee antigen particularity, and yields exceptionally precise expectations of antigen‐specific TCRs.14 Furthermore, GLIPH can coordinate numerous variables remembered for collection information, for example, V quality utilization, CDR3 length, clonal development, and HLA alleles. In this investigation, we intended to explain trademark TCR collections for all α/β/δ/γ chains in MS utilizing next‐generation sequencing, and to distinguish TCRs related with MS pathogenesis by contrasting TCR qualities between Japanese MS patients and sound controls (HCs) utilizing GLIPH. Moreover, given that patients with various HLA alleles show unmistakable illness movement, we additionally meant to look for MS‐associated TCRs that are advanced in a gathering of MS patients with specific MS‐associated HLA‐DRB1 alleles. At last, we portrayed the clinical and immunological highlights of patients with certain MS‐associated TCRs.
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Early predictors of 9‐year disability in pediatric multiple sclerosis - De Meo - - Annals of Neurology

Early predictors of 9‐year disability in pediatric multiple sclerosis - De Meo - - Annals of Neurology | Multiple sclerosis New Drugs Review | Scoop.it
Objectives To assess early predictors of 9‐year disability in pediatric multiple sclerosis patients. Methods Clinical and MRI assessments of 123 pediatric multiple sclerosis patients were obtained ...
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Speech Pathology-Specific Questionnaire for Persons with Multiple Sclerosis (SMS): adaptation, validation and preliminary assessment of the diagnostic potential. - ScienceDirect

Speech Pathology-Specific Questionnaire for Persons with Multiple Sclerosis (SMS): adaptation, validation and preliminary assessment of the diagnostic potential. - ScienceDirect | Multiple sclerosis New Drugs Review | Scoop.it
Highlights

Speech and voice disorders are among the least well-described clinical manifestations of Multiple Sclerosis.


Speech Pathology-Specific Questionnaire for Persons with Multiple Sclerosis (SMS) was developed and validated for the assessment of speech-language pathology in MS patients.


The psychometric properties of the Polish version of SMS Questionnaire indicate a validity of patient-reported outcome for the assessment of speech-language pathology.
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Pharmaceutics | Patient-Derived Induced Pluripotent Stem Cells (iPSCs) and Cerebral Organoids for Drug Screening and Development in Autism Spectrum Disorder: Opportunities and Chal...

Pharmaceutics | Patient-Derived Induced Pluripotent Stem Cells (iPSCs) and Cerebral Organoids for Drug Screening and Development in Autism Spectrum Disorder: Opportunities and Chal... | Multiple sclerosis New Drugs Review | Scoop.it
Autism spectrum disorder (ASD) represents a group of neurodevelopmental diseases characterized by persistent deficits in social communication, interaction, and repetitive patterns of behaviors, interests, and activities.
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Neddylation — a new therapeutic target for multiple sclerosis?

A new transcriptomic study has demonstrated upregulation of genes associated with neddylation — a post-translational protein modification similar to ubiquitylation — in T cells from people with multiple sclerosis (MS). In particular, NAE1, which encodes a subunit of the NEDD8-activating enzyme, was upregulated in CD4+ T cells, and the investigators found that an inhibitor of this enzyme reduced disease severity in a mouse model of MS. The findings suggest that neddylation warrants further exploration as a possible therapeutic target for MS.
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Autologous haematopoietic stem cell transplantation as a first-line disease-modifying therapy in patients with ‘aggressive’ multiple sclerosis - J Das, JA Snowden, J Burman, MS Freedman, H Atkins, ...

Autologous haematopoietic stem cell transplantation as a first-line disease-modifying therapy in patients with ‘aggressive’ multiple sclerosis - J Das, JA Snowden, J Burman, MS Freedman, H Atkins, ... | Multiple sclerosis New Drugs Review | Scoop.it
Background:Autologous haematopoietic stem cell transplantation (AHSCT) is an effective treatment for patients with multiple sclerosis (MS) who have highly active disease, despite the use of standar...
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Serum phospholipidomics reveals altered lipid profile and promising biomarkers in multiple sclerosis - ScienceDirect

Serum phospholipidomics reveals altered lipid profile and promising biomarkers in multiple sclerosis - ScienceDirect | Multiple sclerosis New Drugs Review | Scoop.it
Multiple sclerosis is a neurodegenerative disease causing disability in young adults. Alterations in metabolism and lipid profile have been associated…
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Disruption of the Atrophy-based Functional Network in Multiple Sclerosis Is Associated with Clinical Disability: Validation of a Meta-Analytic Model in Resting-State Functional MRI | Radiology

Disruption of the Atrophy-based Functional Network in Multiple Sclerosis Is Associated with Clinical Disability: Validation of a Meta-Analytic Model in Resting-State Functional MRI | Radiology | Multiple sclerosis New Drugs Review | Scoop.it
In multiple sclerosis, disruption of the atrophy-based functional network is strongly associated with clinical disability, thereby providing support for the network degeneration hypothesis of local...
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IL-17 controls central nervous system autoimmunity through the intestinal microbiome | Science Immunology

IL-17 controls central nervous system autoimmunity through the intestinal microbiome | Science Immunology | Multiple sclerosis New Drugs Review | Scoop.it
Gut reaction to IL-17
Whether IL-17A/F or TH17 cells are necessary for the immunopathogenesis of human multiple sclerosis (MS) has been a topic of active debate. Using experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, in mice deficient for IL-17A and IL-17F, Regen et al. found that IL-17 ablation reduced susceptibility to EAE. However, adoptive transfer of TH17 cells from autoantigen-primed IL-17–deficient mice recapitulated disease in naïve control mice but not in IL-17–deficient mice. Cohousing IL-17–deficient mice with IL-17–expressing mice, fecal transplantation from IL-17–expressing mice into IL-17–deficient mice, and reexpression of IL-17A in the gut of IL-17–deficient mice restored susceptibility to EAE. Thus, IL-17 expression in the gut rather than its effector function in the CNS is directly linked to EAE susceptibility by modulating the gut microbiome.
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Diversity and Function of Glial Cell Types in Multiple Sclerosis - ScienceDirect

Diversity and Function of Glial Cell Types in Multiple Sclerosis - ScienceDirect | Multiple sclerosis New Drugs Review | Scoop.it
Highlights
Single-cell transcriptomic technologies have revolutionized our understanding of homeostatic and reactive glial cell types during disease progression in experimental models and in human multiple sclerosis (MS) tissue samples, which can reflect different stages of tissue damage.

Homeostatic and reactive glial cell types show intra- and inter-regional heterogeneity in different central nervous system (CNS) areas and within inflammatory–demyelinating lesions.

Reactive glial subtypes are highly polarized based on morphological, transcriptomic, and functional criteria, having seemingly opposing roles in either promoting or suppressing inflammation and further tissue damage.

Glial subtype-specific transcriptomic profiling has helped identify novel homeostatic and reactive subtype markers that will be useful for the development of novel biomarkers and therapeutic targets for future studies in MS.
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