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Natalizumab EAE

Begoña M Escribano, Francisco J Medina-Fernández, Macarena Aguilar-Luque, Eduardo Agüera, Montserrat Feijoo, Fe I Garcia-Maceira, Rafael Lillo, Patricia Vieyra-Reyes, Ana I Giraldo, Evelio Luque, René Drucker-Colín, Isaac Túnez
Recent findings in experimental autoimmune encephalomyelitis (EAE) suggest that altering certain bacterial populations present in the gut may lead to a proinflammatory condition, that could result in the development of multiple sclerosis (MS). Also, Reactive Oxygen Species seem to be involved in the course of MS. In this study, it has been aimed to relate all these variables starting from an analysis of the lipopolysaccharide (LPS) and LPS-binding protein (LBP) with the determination of parameters related to oxidative stress in the blood, brain and spinal cord...
October 7, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Elena Boggio, Chiara Dianzani, Casimiro Luca Gigliotti, Maria Felicia Soluri, Nausicaa Clemente, Giuseppe Cappellano, Erika Toth, Davide Raineri, Benedetta Ferrara, Cristoforo Comi, Umberto Dianzani, Annalisa Chiocchetti
Osteopontin is a proinflammatory cytokine and plays a pathogenetic role in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), by recruiting autoreactive T cells into the central nervous system. Osteopontin functions are modulated by thrombin cleavage generating N- and C-terminal fragment, whose individual roles are only partly known. Published data are difficult to compare since they have been obtained with heterogeneous approaches. Interestingly, thrombin cleavage of osteopontin unmasks a cryptic domain of interaction with α 4 β 1 integrin that is the main adhesion molecule involved in lymphocyte transmigration to the brain and is the target for natalizumab, the most potent drug preventing relapses...
2016: Journal of Immunology Research
Beatriz Bravo, Marta I Gallego, Ana I Flores, Rafael Bornstein, Alba Puente-Bedia, Javier Hernández, Paz de la Torre, Elena García-Zaragoza, Raquel Perez-Tavarez, Jesús Grande, Alicia Ballester, Sara Ballester
BACKGROUND: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest...
2016: Stem Cell Research & Therapy
Andre Ortlieb Guerreiro-Cacais, Hannes Laaksonen, Sevasti Flytzani, Marie N'diaye, Tomas Olsson, Maja Jagodic
Multiple sclerosis (MS) is a complex autoimmune condition with firmly established genetic and environmental components. Genome-wide association studies (GWAS) have revealed a large number of genetic polymorphisms in the vicinity of, and within, genes that associate to disease. However, the significance of these single-nucleotide polymorphisms in disease and possible mechanisms of action remain, with a few exceptions, to be established. While the animal model for MS, experimental autoimmune encephalomyelitis (EAE), has been instrumental in understanding immunity in general and mechanisms of MS disease in particular, much of the translational information gathered from the model in terms of treatment development (glatiramer acetate and natalizumab) has been extensively summarized...
2015: Journal of Inflammation Research
Nourollah Ramroodi, Masood Khani, Zohre Ganjali, Mohammad Reza Javan, Nima Sanadgol, Roghayeh Khalseh, Hadi Ravan, Ehsan Sanadgol, Mohammad Abdollahi
BACKGROUND AND PURPOSE: Some functional limitations and economic burden of therapeutic antibodies indicated that introducing of alternative therapeutic compounds with same or different mechanism of action could be worthwhile. In this regard small-molecule antagonists can have a wide range of impacts, so in this research, we examine the prophylactic effects of BIO-1211 [Very Late Antigen-4 (VLA4) blocker], in experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis in comparison with commercial available medicine, Natalizumab (NTZ)]...
2015: Immunological Investigations
Kristina Candido, Henry Soufi, Mausumi Bandyopadhyay, Subhajit Dasgupta
Multiple sclerosis (MS) is a female predominant autoimmune demyelinating disease of central nervous system. The proper etiology is not clear. The existing therapies with interferon beta (Betaseron, Rebif), glatiramer acetate (copolymer 1, copaxone) are found to be promising for MS patients. The alpha-4 integrin antagonist monoclonal antibody Natalizumab has been found to decrease brain inflammation in relapsing-remitting MS via inhibition of alpha-4 beta- 1 integrinmediated mode of action of antigen -primed T cells to enter into central nervous system through blood brain barrier...
2016: Mini Reviews in Medicinal Chemistry
Jens Ingwersen, Til Menge, Britta Wingerath, Derya Kaya, Jonas Graf, Tim Prozorovski, Andreas Keller, Christina Backes, Markus Beier, Matthias Scheffler, Thomas Dehmel, Bernd C Kieseier, Hans-Peter Hartung, Patrick Küry, Orhan Aktas
OBJECTIVE: To identify microRNAs (miRNAs) regulated by anti-α4 integrin monoclonal antibody therapy (natalizumab) in the peripheral blood of patients with relapsing-remitting (RR) multiple sclerosis (MS) and to confirm their role in experimental settings in vivo. METHODS: In a longitudinal study of 17 RR-MS patients, we investigated blood miRNA expression profiles at baseline and after 1 year of natalizumab therapy by microarray technique and quantitative PCR validation...
January 2015: Annals of Clinical and Translational Neurology
Tohid Gharibi, Majid Ahmadi, Narges Seyfizadeh, Farhad Jadidi-Niaragh, Mehdi Yousefi
Multiple Sclerosis (MS) is a chronic inflammatory neurodegenerative disease of central nervous system (CNS). Although the main cause of MS is not clear, studies suggest that MS is an autoimmune disease which attacks myelin sheath of neurons. There are different therapeutic regimens for MS patients including interferon (IFN)-β, glatiramer acetate (GA), and natalizumab. However, such therapies are not quite effective and are associated with some side effects. So which, there is no complete therapeutic method for MS patients...
February 2015: Cellular Immunology
Lawrence Steinman, Yehuda Shoenfeld
Ruth Arnon and Michael Sela profoundly influenced the development of a model system to test new therapies in multiple sclerosis (MS). Their application of the animal model, known as experimental autoimmune encephalomyelitis (EAE), for the discovery of Copaxone, opened a new path for testing of drug candidates in MS. By measuring clinical, pathologic, and immunologic outcomes, the biological implications of new drugs could be elucidated. Using EAE they established the efficacy of Copaxone as a therapy for preventing and reducing paralysis and inflammation in the central nervous system without massive immune suppression...
November 2014: Journal of Autoimmunity
Michael K Racke, Yuhong Yang, Amy E Lovett-Racke
Treatments for multiple sclerosis (MS) have changed over the past years as our understanding of immunology and neuroscience has evolved. Experimental autoimmune encephalomyelitis (EAE) continues to remain the major model for MS and has been a major vehicle in the development of new therapeutic targets for MS, including new agents such as natalizumab, fingolimod, and dimethyl fumarate. As progress in the molecular understanding of immunology continues, many observations in EAE are pursued with the ultimate goal of defining the pathophysiology of MS and development of innovative treatments for the disease...
August 2014: Journal of Interferon & Cytokine Research
John E Mindur, Naoko Ito, Suhayl Dhib-Jalbut, Kouichi Ito
Natalizumab is a humanized monoclonal antibody against the leukocyte adhesion molecule very late antigen (VLA)-4, and is currently an approved therapy for patients with relapsing-remitting multiple sclerosis (RRMS). However, it is unknown whether natalizumab is beneficial for progressive forms of MS. Therefore, we assessed the effects of anti-VLA-4 monoclonal antibody (mAb) therapy in a progressive experimental autoimmune encephalomyelitis (EAE) mouse model. Notably, we found that early therapy could significantly reduce the severity of progressive EAE, while treatment initiated at an advanced stage was less efficient...
2014: PloS One
Andrew P Robinson, Christopher T Harp, Avertano Noronha, Stephen D Miller
While no single model can exactly recapitulate all aspects of multiple sclerosis (MS), animal models are essential in understanding the induction and pathogenesis of the disease and to develop therapeutic strategies that limit disease progression and eventually lead to effective treatments for the human disease. Several different models of MS exist, but by far the best understood and most commonly used is the rodent model of experimental autoimmune encephalomyelitis (EAE). This model is typically induced by either active immunization with myelin-derived proteins or peptides in adjuvant or by passive transfer of activated myelin-specific CD4+ T lymphocytes...
2014: Handbook of Clinical Neurology
Ghazal Banisadr, Samantha R Schwartz, Joseph R Podojil, Linda A Piccinini, Stefan Lanker, Stephen D Miller, Richard J Miller
Excessive infiltration of leukocytes and the elaboration of inflammatory cytokines are believed to be responsible for the observed damage to neurons and oligodendrocytes during multiple sclerosis (MS). Blocking adhesion molecules or preventing the effects of chemotactic mediators such as chemokines can be exploited to prevent immune cell recruitment to inflamed tissues. An anti-α4 integrin antibody (anti-VLA-4mAb/natalizumab (Tysabri®)) has been used as a treatment for MS and reduces leukocyte influx into the brain...
June 2014: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Erik Wright, Kusha Rahgozar, Nicholas Hallworth, Stefan Lanker, Michael D Carrithers
Natalizumab inhibits the transmigration of activated T lymphocytes into the brain and is highly efficacious in multiple sclerosis (MS). However, from a pharmacogenomic perspective, its efficacy and safety in specific patients remain unclear. Here our goal was to analyze the effects of epithelial V-like antigen (EVA) on anti-alpha₄ integrin (VLA4) efficacy in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EVA has been previously characterized in human CD4 T lymphocytes, mouse thymic development, and choroid plexus epithelial cells...
2013: PloS One
Violaine K Harris, Nicola Donelan, Qi Jiang Yan, Kristi Clark, Amir Touray, Mustapha Rammal, Saud A Sadiq
BACKGROUND: There is an urgent need for biomarkers in multiple sclerosis (MS) that can reliably measure ongoing disease activity relative to inflammation, neurodegeneration, and demyelination/remyelination. Fetuin-A was recently identified as a potential biomarker in MS cerebrospinal fluid (CSF). Fetuin-A has diverse functions, including a role in immune pathways. OBJECTIVE: The objective of this research is to investigate whether fetuin-A is a direct indicator of disease activity...
October 2013: Multiple Sclerosis: Clinical and Laboratory Research
Fernanda Marques, Sandro D Mesquita, João C Sousa, Giovanni Coppola, Fuying Gao, Daniel H Geschwind, Sandra Columba-Cabezas, Francesca Aloisi, Matilda Degn, João J Cerqueira, Nuno Sousa, Margarida Correia-Neves, Joana A Palha
Multiple sclerosis (MS) is a demyelinating disease that causes major neurological disability in young adults. A definitive diagnosis at the time of the first episode is still lacking, but since early treatment leads to better prognosis, the search for early biomarkers is needed. Here we characterized the transcriptome of the choroid plexus (CP), which is part of the blood-brain barriers (BBBs) and the major site of cerebrospinal fluid production, in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS...
2012: Frontiers in Cellular Neuroscience
Yan Gan, Ruolan Liu, Wei Wu, Roberto Bomprezzi, Fu-Dong Shi
Natalizumab inhibits the influx of leukocytes into the central nervous system (CNS) via blockade of alpha-4 subunit of very late activation antigen (VLA)-4. The association of natalizumab therapy with progressive multifocal leukoencephalopathy (PML) suggests a disturbance of CNS immune surveillance in a small percentage of Multiple Sclerosis (MS) patients exposed to the medication. Natural killer (NK) cells are known to play an important role in modulating the evolution of different phases of this lymphocyte mediated disease, and we investigated the effects of natalizumab on the NK cell phenotype and infiltration in the CNS in experimental autoimmune encephalomyelitis (EAE), a murine model of MS...
June 15, 2012: Journal of Neuroimmunology
Axinia Döring, Friederike Pfeiffer, Matthias Meier, Bénédicte Dehouck, Silke Tauber, Urban Deutsch, Britta Engelhardt
Inhibiting the α4 subunit of the integrin heterodimers α4β1 and α4β7 with the mab natalizumab is an effective treatment of multiple sclerosis (MS). Which of the two α4 heterodimers is involved in disease pathogenesis has, however, remained controversial. Whereas the development of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, is ameliorated in β7-integrin-deficient C57BL/6 mice, neutralizing antibodies against the β7-integrin subunit or the α4β7-integrin heterodimer fail to interfere with EAE pathogenesis in the SJL mouse...
March 2011: European Journal of Immunology
Aleksandar Denic, Aaron J Johnson, Allan J Bieber, Arthur E Warrington, Moses Rodriguez, Istvan Pirko
Multiple Sclerosis (MS) is a complex disease with an unknown etiology and no effective cure, despite decades of extensive research that led to the development of several partially effective treatments. Researchers have only limited access to early and immunologically active MS tissue samples, and the modification of experimental circumstances is much more restricted in human studies compared to studies in animal models. For these reasons, animal models are needed to clarify the underlying immune-pathological mechanisms and test novel therapeutic and reparative approaches...
February 2011: Pathophysiology: the Official Journal of the International Society for Pathophysiology
Ralf A Linker, De-Hyung Lee
Multiple sclerosis (MS) is the most common neurologic disease of young adults. In the recent years, our understanding on disease pathomechanisms has considerably improved and new therapies have emerged. Yet a cure for this devastating disorder is still a far cry away and human resources on ex vivo specimens are limited. More than 70 years after its first description, experimental autoimmune encephalomyelitis (EAE) remains an important tool to understand concepts of T cell mediated autoimmunity as well as the roles of the innate and the humoral immune systems...
2009: Experimental & Translational Stroke Medicine
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