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Progressive multiple sclerosis treatment

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https://www.readbyqxmd.com/read/29143589/biomarkers-in-the-evolution-of-multiple-sclerosis
#1
Thomas Berger
Nonimaging biomarkers can be applied in differential diagnosis, evaluation of disease progression and therapy monitoring of multiple sclerosis (MS). Presence of oligoclonal IgG bands in cerebrospinal fluid is a diagnostic element and a negative predictor of MS evolution. AQP4 antibodies are pathogenic and diagnostic for neuromyelitis optica spectrum disorder. Antibodies to myelin oligodendrocyte glycoprotein develop in about 50% of predominantly pediatric patients with acute disseminated encephalomyelitis, but their possible role in pathogenesis is unknown...
November 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/29143582/personalized-medicine-in-multiple-sclerosis
#2
Gavin Giovannoni
The therapeutic approach in multiple sclerosis (MS) requires a personalized medicine frame beyond the precision medicine concept, which is not currently implementable due to the lack of robust biomarkers and detailed understanding of MS pathogenesis. Personalized medicine demands a patient-focused approach, with disease taxonomy informed by characterization of pathophysiological processes. Important questions concerning MS taxonomy are: when does MS begin? When does the progressive phase begin? Is MS really two or three diseases? Does a therapeutic window truly exist? Newer evidence points to a disease spectrum and a therapeutic lag of several years for benefits to be observed from disease-modifying therapy...
November 2017: Neurodegenerative Disease Management
https://www.readbyqxmd.com/read/29143287/lipoic-acid-stimulates-camp-production-in-healthy-control-and-secondary-progressive-ms-subjects
#3
Sarah E Fiedler, Vijayshree Yadav, Amelia R Kerns, Catherine Tsang, Sheila Markwardt, Edward Kim, Rebecca Spain, Dennis Bourdette, Sonemany Salinthone
Lipoic acid (LA) exhibits antioxidant and anti-inflammatory properties; supplementation reduces disease severity and T lymphocyte migration into the central nervous system in a murine model of multiple sclerosis (MS), and administration in secondary progressive MS (SPMS) subjects reduces brain atrophy compared to placebo. The mechanism of action (MOA) of LA's efficacy in suppression of MS pathology is incompletely understood. LA stimulates production of the immunomodulator cyclic AMP (cAMP) in vitro. To determine whether cAMP could be involved in the MOA of LA in vivo, we performed a clinical trial to examine whether LA stimulates cAMP production in healthy control and MS subjects, and whether there are differences in the bioavailability of LA between groups...
November 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29143164/upregulation-of-myelin-gene-expression-by-a-physically-modified-saline-via-phosphatidylinositol-3-kinase-mediated-activation-of-creb-implications-for-multiple-sclerosis
#4
Malabendu Jana, Supurna Ghosh, Kalipada Pahan
An increase in central nervous system (CNS) remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis (MS). RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60 exhibits anti-inflammatory properties. Here, we describe promyelinating property of RNS60. RNS60, but not normal saline (NS), RNS10.3 (TCP-modified saline without excess oxygen) or PNS60 (saline containing excess oxygen without TCP modification), stimulated the expression of myelin-specific genes and proteins (myelin basic protein, MBP; myelin oligodendrocyte glycoprotein, MOG and proteolipid protein, PLP) in primary mouse oligodendroglia and mixed glial cells...
November 15, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29141822/epidemiological-and-clinical-characteristics-of-multiple-sclerosis-in-paediatric-population-in-slovenia-a-descriptive-nation-wide-study
#5
Neli Bizjak, Damjan Osredkar, Mirjana Perković Benedik, Saša Šega Jazbec
BACKGROUND: Although multiple sclerosis usually affects young adults, paediatric-onset multiple sclerosis (pMS) is increasingly recognized in the past ten years. The aim of the present study was to evaluate the incidence of pMS in Slovenia and to characterize the clinical, laboratory and neuroradiological characteristics of pMS at the disease onset. METHODS: We performed a national retrospective descriptive study including all patients diagnosed with pMS between January 1992 and June 2017...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29141796/high-dose-biotin-as-treatment-for-progressive-multiple-sclerosis
#6
Gary Birnbaum, Jessica Stulc
BACKGROUND: Published data suggested high dose biotin improved patients with progressive MS. We wished to determine benefits and side effects of administering daily high dose biotin to patients with progressive multiple sclerosis in a large MS specialty clinic. METHODS: Forty-three patients with progressive multiple scleroses were prescribed pharmaceutical grade biotin as a single daily dose of 300mg/day. Brain MRIs were performed at baseline and after one year on biotin...
November 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29138536/spotlight-on-siponimod-and-its-potential-in-the-treatment-of-secondary-progressive-multiple-sclerosis-the-evidence-to-date
#7
REVIEW
Alberto Gajofatto
Siponimod (BAF312) is a synthetic molecule belonging to the sphingosine-1-phosphate (S1P) modulator family, which has putative neuroprotective properties and well-characterized immunomodulating effects mediated by sequestration of B and T cells in secondary lymphoid organs. Compared to fingolimod (ie, precursor of the S1P modulators commercially available for the treatment of relapsing-remitting [RR] multiple sclerosis [MS]), siponimod exhibits selective affinity for types 1 and 5 S1P receptor, leading to a lower risk of adverse events that are mainly induced by S1P3 receptor activation, such as bradycardia and vasoconstriction...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29137922/extracellular-vesicles-in-neurodegenerative-diseases
#8
REVIEW
Tommaso Croese, Roberto Furlan
Extracellular vesicles (EVs) are released by all neural cells, including neurons, oligodendrocytes, astrocytes, and microglia. The lack of adequate technology has not halted neuroscientists from investigating EVs as a mean to decipher neurodegenerative disorders, still in search of comprehensible pathogenic mechanisms and efficient treatment. EVs are thought to be one of ways neurodegenerative pathologies spread in the brain, but also one of the ways the brain tries to displace toxic proteins, making their meaning in pathogenesis uncertain...
November 11, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29132838/therapeutic-effects-of-diosgenin-in-experimental-autoimmune-encephalomyelitis
#9
Weili Liu, Mei Zhu, Zhongwang Yu, Dou Yin, Fengfeng Lu, Yingyan Pu, Chao Zhao, Cheng He, Li Cao
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system. Currently, there is no drug available to cure this kind of disease. Diosgenin is a plant-derived steroid saponin. A previous study in our lab revealed that diosgenin can promote oligodendrocyte progenitor cell differentiation and accelerate remyelination. In the present study, we found that diosgenin dose-dependently alleviated the progression of experimental autoimmune encephalomyelitis with reduced central nervous system inflammation and demyelination...
October 31, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29132538/immunometabolic-profiling-of-t-cells-from-patients-with-relapsing-remitting-multiple-sclerosis-reveals-an-impairment-in-glycolysis-and-mitochondrial-respiration
#10
Claudia La Rocca, Fortunata Carbone, Veronica De Rosa, Alessandra Colamatteo, Mario Galgani, Francesco Perna, Roberta Lanzillo, Vincenzo Brescia Morra, Giuseppe Orefice, Ilaria Cerillo, Ciro Florio, Giorgia Teresa Maniscalco, Marco Salvetti, Diego Centonze, Antonio Uccelli, Salvatore Longobardi, Andrea Visconti, Giuseppe Matarese
BACKGROUND: Metabolic reprogramming is shaped to support specific cell functions since cellular metabolism controls the final outcome of immune response. Multiple sclerosis (MS) is an autoimmune disease resulting from loss of immune tolerance against central nervous system (CNS) myelin. Metabolic alterations of T cells occurring during MS are not yet well understood and their studies could have relevance in the comprehension of the pathogenetic events leading to loss of immune tolerance to self and to develop novel therapeutic strategies aimed at limiting MS progression...
December 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29128737/a-8-year-retrospective-cohort-study-comparing-interferon-%C3%AE-formulations-for-relapsing-remitting-multiple-sclerosis
#11
Marcello Moccia, Raffaele Palladino, Antonio Carotenuto, Francesco Saccà, Cinzia Valeria Russo, Roberta Lanzillo, Vincenzo Brescia Morra
BACKGROUND: Interferon-β has been approved for the treatment of relapsing-remitting (RR) multiple sclerosis (MS), whereas its efficacy in preventing long-term disability and conversion to secondary progressive (SP) MS is still debated. We aim to compare long-term clinical evolution of newly-diagnosed RRMS patients treated with different Interferon-β formulations. METHODS: 507 patients were included in the analysis and followed-up for 8.5 ± 3.9 years. 37.6% were treated with subcutaneous Interferon-β1a 44mcg, 33...
November 6, 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/29128442/urinary-excretion-of-aluminium-and-silicon-in-secondary-progressive-multiple-sclerosis
#12
Krista Jones, Caroline Linhart, Clive Hawkins, Christopher Exley
BACKGROUND: Progressive multiple sclerosis is a chronic autoimmune condition of unknown aetiology and few therapeutic options. Human exposure to aluminium has been linked with multiple sclerosis and affected individuals are known to excrete unusually high amounts of aluminium in their urine. Silicon-rich mineral waters facilitate the removal of aluminium from the body in urine and herein we have tested their efficacy in affecting urinary excretion of aluminium in individuals diagnosed with secondary progressive multiple sclerosis (SPMS)...
November 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/29127843/ifn-%C3%AE-regulates-th17-differentiation-partly-through-the-inhibition-of-osteopontin-in-experimental-autoimmune-encephalomyelitis
#13
Qing Zhao, Wenjing Cheng, Yebin Xi, Zheyi Cao, Yunzhi Xu, Ting Wu, Chengzhen Li, Xiaoyin Niu, Guangjie Chen
Multiple sclerosis (MS) and the corresponding animal model, experimental autoimmune encephalomyelitis (EAE), are chronic neuroinflammatory autoimmune diseases. Increased activation of CD4+T cells, especially the Th1 and Th17 subsets, is thought to play a causal role in this disease. IFN-β is widely used in the treatment of MS and is found to decrease IL-17 and OPN production in MS patients and EAE mice. However, a definitive molecular mechanism has not yet been fully elucidated. In this study, we investigated the immunomodulatory effect of IFN-β on the EAE model...
November 7, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29123469/suppression-of-inflammatory-demyelinaton-and-axon-degeneration-through-inhibiting-kv3-channels
#14
Peter Jukkola, Yuanzheng Gu, Amy E Lovett-Racke, Chen Gu
The development of neuroprotective and repair strategies for treating progressive multiple sclerosis (MS) requires new insights into axonal injury. 4-aminopyridine (4-AP), a blocker of voltage-gated K(+) (Kv) channels, is used in symptomatic treatment of progressive MS, but the underlying mechanism remains unclear. Here we report that deleting Kv3.1-the channel with the highest 4-AP sensitivity-reduces clinical signs in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In Kv3.1 knockout (KO) mice, EAE lesions in sensory and motor tracts of spinal cord were markedly reduced, and radial astroglia were activated with increased expression of brain derived neurotrophic factor (BDNF)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29119538/safety-and-effectiveness-of-natalizumab-first-report-of-interim-results-of-post-marketing-surveillance-in-japan
#15
Takahiko Saida, Kazumasa Yokoyama, Ryusuke Sato, Haruki Makioka, Yukihiko Iizuka, Masakazu Hase, Yan Ling, Shinichi Torii
INTRODUCTION: Natalizumab, a humanized anti-α4 integrin monoclonal antibody, received marketing approval in Japan in 2014 for the treatment of multiple sclerosis (MS). Because the previous large-scale clinical trials of natalizumab were mainly conducted in Europe and North American countries, and data in patients with MS from Japan were limited, we conducted an all-case post-marketing surveillance of natalizumab-treated MS patients from Japan to investigate the safety and effectiveness of natalizumab in a real-world clinical setting in Japan...
November 8, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/29116612/the-complement-system-as-a-biomarker-of-disease-activity-and-response-to-treatment-in-multiple-sclerosis
#16
REVIEW
Alexandru Tatomir, Anamaria Talpos-Caia, Freidrich Anselmo, Adam M Kruszewski, Dallas Boodhoo, Violeta Rus, Horea Rus
Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system. The complement system has an established role in the pathogenesis of MS, and evidence suggests that its components can be used as biomarkers of disease-state activity and response to treatment in MS. Plasma C4a levels have been found to be significantly elevated in patients with active relapsing-remitting MS (RRMS), as compared to both controls and patients with stable RRMS. C3 levels are also significantly elevated in the cerebrospinal fluid (CSF) of patients with RRMS, and C3 levels are correlated with clinical disability...
November 8, 2017: Immunologic Research
https://www.readbyqxmd.com/read/29114087/the-cooling-compound-icilin-attenuates-autoimmune-neuroinflammation-through-modulation-of-the-t-cell-response
#17
Benjamin W Ewanchuk, Euan R O Allan, Amy L Warren, Rithwik Ramachandran, Robin M Yates
The synthetic supercooling drug, icilin, and its primary receptor target, the cation channel transient receptor potential (TRP) melastatin-8 (TRPM8), have been described as potent negative regulators of inflammation in the colon. The aim of this study was to determine whether the anti-inflammatory action of icilin could potentially be used to treat autoimmune neuroinflammatory disorders, such as multiple sclerosis (MS). During experimental autoimmune encephalomyelitis (EAE)-a CD4(+) T cell-driven murine model of MS-we found that both wild-type (WT) and TRPM8-deficient EAE mice were protected from disease progression during icilin treatment, as evidenced by delays in clinical onset and reductions in neuroinflammation...
November 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29112130/role-of-immunological-memory-cells-as-a-therapeutic-target-in-multiple-sclerosis
#18
REVIEW
Tanima Bose
Pharmacological targeting of memory cells is an attractive treatment strategy in various autoimmune diseases, such as psoriasis and rheumatoid arthritis. Multiple sclerosis is the most common inflammatory disorder of the central nervous system, characterized by focal immune cell infiltration, activation of microglia and astrocytes, along with progressive damage to myelin sheaths, axons, and neurons. The current review begins with the identification of memory cell types in the previous literature and a recent description of the modulation of these cell types in T, B, and resident memory cells in the presence of different clinically approved multiple sclerosis drugs...
November 7, 2017: Brain Sciences
https://www.readbyqxmd.com/read/29108879/remyelination-modulators-in-multiple-sclerosis-patients
#19
Rabeah Al-Temaimi, Jehad AbuBaker, Irina Al-Khairi, Raed Alroughani
Multiple Sclerosis (MS) is a complex autoimmune neuro-inflammatory disorder characterized by persistent MS plaques in the central nervous system. Resolution of MS plaques is dependent on the remyelination competence of surviving oligodendrocytes and surrounding environment. Here, we assessed myelination modulators in a 100 MS patients against 77 healthy controls. Plasma fractions were used for the assessment of insulin growth factor binding protein1 (IGFBP1), brain-derived neurotrophic factor (BDNF), and lipocalin2 (LCN2) using a Luminex multiplex assay, whereas neurofilament light chain (NF-L) was assessed with an enzyme-linked immunosorbent assay...
November 8, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29107957/febuxostat-ameliorates-secondary-progressive-experimental-autoimmune-encephalomyelitis-by-restoring-mitochondrial-energy-production-in-a-got2-dependent-manner
#20
Josephe A Honorat, Yuji Nakatsuji, Mikito Shimizu, Makoto Kinoshita, Hisae Sumi-Akamaru, Tsutomu Sasaki, Kazushiro Takata, Toru Koda, Akiko Namba, Kazuya Yamashita, Eri Sanda, Manabu Sakaguchi, Atsushi Kumanogoh, Takashi Shirakura, Mizuho Tamura, Saburo Sakoda, Hideki Mochizuki, Tatsusada Okuno
Oxidative stress and mitochondrial dysfunction are important determinants of neurodegeneration in secondary progressive multiple sclerosis (SPMS). We previously showed that febuxostat, a xanthine oxidase inhibitor, ameliorated both relapsing-remitting and secondary progressive experimental autoimmune encephalomyelitis (EAE) by preventing neurodegeneration in mice. In this study, we investigated how febuxostat protects neuron in secondary progressive EAE. A DNA microarray analysis revealed that febuxostat treatment increased the CNS expression of several mitochondria-related genes in EAE mice, most notably including GOT2, which encodes glutamate oxaloacetate transaminase 2 (GOT2)...
2017: PloS One
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