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Progressive multiple sclerosis treatment

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https://www.readbyqxmd.com/read/28917696/brain-mapping-in-multiple-sclerosis-lessons-learned-about-the-human-brain
#1
REVIEW
Massimo Filippi, Paolo Preziosa, Maria A Rocca
The application of structural and functional magnetic resonance imaging (MRI) techniques in patients with multiple sclerosis (MS) has certainly helped to improve our understanding of the mechanisms responsible for clinical disability and cognitive impairment in this condition. The numerous studies performed in MS patients have also provided many lessons on the structure-function relationships in the human brain, which could be applied to healthy subjects and to patients affected by other neurological conditions...
September 13, 2017: NeuroImage
https://www.readbyqxmd.com/read/28914229/clinical-effectiveness-and-cost-effectiveness-of-beta-interferon-and-glatiramer-acetate-for-treating-multiple-sclerosis-systematic-review-and-economic-evaluation
#2
G J Melendez-Torres, Peter Auguste, Xavier Armoiry, Hendramoorthy Maheswaran, Rachel Court, Jason Madan, Alan Kan, Stephanie Lin, Carl Counsell, Jacoby Patterson, Jeremy Rodrigues, Olga Ciccarelli, Hannah Fraser, Aileen Clarke
BACKGROUND: At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. OBJECTIVES: To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other...
September 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28913765/treatment-of-theiler-s-virus-induced-demyelinating-disease-with-teriflunomide
#3
Francesca Gilli, Libin Li, Darlene B Royce, Krista D DiSano, Andrew R Pachner
Teriflunomide is an oral therapy approved for the treatment of relapsing remitting multiple sclerosis (MS), showing both anti-inflammatory and antiviral properties. Currently, it is uncertain whether one or both of these properties may explain teriflunomide's beneficial effect in MS. Thus, to learn more about its mechanisms of action, we evaluated the effect of teriflunomide in the Theiler's encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) model, which is both a viral infection and an excellent model of the progressive disability of MS...
September 14, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28913726/diagnosis-and-treatment-of-progressive-multifocal-leukoencephalopathy-associated-with-multiple-sclerosis-therapies
#4
REVIEW
Eric M L Williamson, Joseph R Berger
Progressive multifocal leukoencephalopathy (PML) is a rare, but serious, complication encountered in patients treated with a select number of disease-modifying therapies (DMTs) utilized in treating multiple sclerosis (MS). PML results from a viral infection in the brain for which the only demonstrated effective therapy is restoring the perturbed immune system-typically achieved in the patient with MS by removing the offending therapeutic agent or, in the case of HIV-associated PML, treatment with highly active antiretroviral therapies...
September 14, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28910968/efficiency-of-antibody-therapy-in-demyelinating-diseases
#5
Tetsuya Akaishi, Ichiro Nakashima
Monoclonal antibody therapy is a new treatment strategy for many types of diseases including cancers and autoimmune diseases, realizing a high efficacy and tolerability. In multiple sclerosis (MS) and neuromyelitis optica (NMO) spectrum disorders, several monoclonal antibodies have been suggested to decrease the incidence of clinical relapse and the disease activity. In MS, anti-α4 integrin (natalizumab), anti-CD52 (alemtuzumab), anti-CD25 (daclizumab) and anti-CD20 (ocrelizumab) have been shown to effectively reduce the relapses in randomized controlled trials and have been approved by the Food and Drug Administration...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28905255/benefit-risk-profile-of-sphingosine-1-phosphate-receptor-modulators-in-relapsing-and-secondary-progressive-multiple-sclerosis
#6
Giancarlo Comi, Hans-Peter Hartung, Rajesh Bakshi, Ian M Williams, Heinz Wiendl
Since the approval of fingolimod, several selective sphingosine-1-phosphate receptor modulators have entered clinical development for multiple sclerosis. However, side effects can occur with sphingosine-1-phosphate receptor modulators. By considering short-term data across the drug class and longer term fingolimod data, we aim to highlight the potential of sphingosine-1-phosphate receptor modulators in multiple sclerosis, while offering reassurance that their benefit-risk profiles are suitable for long-term therapy...
September 13, 2017: Drugs
https://www.readbyqxmd.com/read/28903387/hyperactivated-mtorc1-downregulation-of-foxo3a-pdgfr%C3%AE-akt-cascade-restrains-tuberous-sclerosis-complex-associated-tumor-development
#7
Li Wang, Zhaofei Ni, Yujie Liu, Shuang Ji, Fuquan Jin, Keguo Jiang, Junfang Ma, Cuiping Ren, Hongbing Zhang, Zhongdong Hu, Xiaojun Zha
Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss-of-function mutations in either the TSC1 or TSC2 gene, leads to the development of tuberous sclerosis complex (TSC), a benign tumor syndrome with multiple affected organs. mTORC1-mediated inhibition of AKT constrains the tumor progression of TSC, but the exact mechanisms remain unclear. Herein we showed that loss of TSC1 or TSC2 downregulation of platelet-derived growth factor receptor α (PDGFRα) expression was mediated by mTORC1...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901547/cognitive-functioning-following-one-year-natalizumab-treatment-a-non-randomized-clinical-trial
#8
I Rorsman, C Petersen, P C Nilsson
OBJECTIVES: Cognitive impairment is common in multiple sclerosis (MS) and can have serious impact on social and occupational functioning. Natalizumab reduces relapse rates, magnetic resonance imaging (MRI) lesions, and progression of disability. Previous studies on cognitive functioning have not based inclusion on cognitive performance criteria. The aim of the present study was to determine any potential natalizumab-related cognitive effects on MS patients performing below normal limits on neuropsychological testing...
September 13, 2017: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/28900067/-dimethyl-fumarate-in-multiple-sclerosis
#9
Masami Tanaka, Yuko Shimizu
At the end of 2016, dimethyl fumarate (DMF) was approved as the sixth disease-modifying drug for multiple sclerosis by the Pharmaceuticals and Medical Devices Agency of Japan. Two randomized, placebo-controlled, phase III studies (DEFINE and CONFIRM) showed beneficial effects in patients in Western countries, with relapsing-remitting multiple sclerosis (RRMS). Some of the benefits included a decreased annual relapse rate, inhibition of disease activity (shown using brain magnetic resonance imaging), and a decreased proportion of patients with confirmed disease progression...
September 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28899916/gd1a-overcomes-inhibition-of-myelination-by-fibronectin-via-activation-of-protein-kinase-a-implications-for-multiple-sclerosis
#10
Jing Qin, Arend H Sikkema, Kristine van der Bij, Jenny C de Jonge, Karin Klappe, Vera Nies, Johan W Jonker, Jan Willem Kok, Dick Hoekstra, Wia Baron
Remyelination failure by oligodendrocytes contributes to the functional impairment that characterizes the demyelinating disease multiple sclerosis (MS). Since incomplete remyelination will irreversibly damage axonal connections, treatments effectively promoting remyelination are pivotal in halting disease progression. Our previous findings suggest that fibronectin aggregates, as an environmental factor, contribute to remyelination failure by perturbing oligodendrocyte progenitor cell (OPC) maturation. Here, we aim at elucidating whether exogenously added gangliosides, i...
September 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28899788/the-translocator-protein-ligand-xbd173-improves-clinical-symptoms-and-neuropathological-markers-in-the-sjl-j-mouse-model-of-multiple-sclerosis
#11
Géraldine Leva, Christian Klein, Jérémie Benyounes, François Hallé, Frédéric Bihel, Nicolas Collongues, Jérôme De Seze, Ayikoe-Guy Mensah-Nyagan, Christine Patte-Mensah
Multiple sclerosis (MS) is a severe autoimmune disease characterized by inflammatory, demyelinating and neurodegenerative components causing motor, sensory, visual and/or cognitive symptoms. The relapsing-remitting MS affecting 85% of patients is reliably mimicked by the proteolipid-protein (PLP)-induced experimental autoimmune encephalomyelitis (EAE) SJL/J-mouse model. Significant progress was made for MS treatment but the development of effective therapies devoid of severe side-effects remains a great challenge...
September 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28899203/an-overview-of-the-advantages-of-keap1-nrf2-system-activation-during-inflammatory-disease-treatment
#12
Nadine Keleku-Lukwete, Mikiko Suzuki, Masayuki Yamamoto
Inflammation can be defined as a protective immune response against harmful exogenous and endogenous stimuli. Nevertheless, prolonged or autoimmune inflammatory response are likely to cause pathological states associated with a production of inflammation-associated molecules along with ROS (reactive oxygen species). KEAP1-NRF2 (Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2) signaling provides a cell protection mechanism against oxidative insults when endogenous stress defense mechanisms are imbalanced...
September 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28894553/effect-of-alpha-lipoic-acid-on-asymmetric-dimethylarginine-and-disability-in-multiple-sclerosis-patients-a-randomized-clinical-trial
#13
Mohammad Khalili, Madjid Soltani, Shirin Amiri Moghadam, Parvin Dehghan, Amirreza Azimi, Omid Abbaszadeh
BACKGROUND: Multiple Sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system. Oxidative stress plays a major role in the onset and progression of MS. Asymmetric dimethylarginine (ADMA) formation is dependent on oxidative stress status. OBJECTIVE: We examined whether alpha-lipoic acid (ALA) as a potent antioxidant could improve the Expanded Disability Status Scale (EDSS) and decrease plasma level of ADMA in multiple sclerosis patients...
July 2017: Electronic Physician
https://www.readbyqxmd.com/read/28875861/therapeutic-monoclonal-antibodies-and-multiple-sclerosis-the-essentials
#14
Ioannis Heliopoulos, Athanasia Patousi
BACKGROUND: Monoclonal antibodies (mAbs) are now established as targeted therapies for malignancies, transplant rejection, autoimmune and infectious diseases. Two monoclonal antibodies are available for treatment and other antibodies are currently being tested in multiple sclerosis (MS) patients. OBJECTIVES: The purpose of the present review paper is to outline the antibody engineering technologies, the immunologic and pharmacologic concepts of mΑbs and the current status of treatment in MS with emphasis on clinical efficacy and safety...
September 6, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28871238/overcoming-therapeutic-inertia-in-multiple-sclerosis-care-a-pilot-randomized-trial-applying-the-traffic-light-system-in-medical-education
#15
Gustavo Saposnik, Jorge Maurino, Angel P Sempere, Maria A Terzaghi, Christian C Ruff, Muhammad Mamdani, Philippe N Tobler, Xavier Montalban
BACKGROUND: Physicians often do not initiate or intensify treatments when clearly warranted, a phenomenon known as therapeutic inertia (TI). Limited information is available on educational interventions to ameliorate knowledge-to-action gaps in TI. OBJECTIVES: To evaluate the feasibility and efficacy of an educational intervention compared to usual care among practicing neurologists caring for patients with multiple sclerosis (MS). METHODS: We conducted a pilot double-blind, parallel-group, randomized clinical trial...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28870585/medical-decision-making-capacity-and-its-cognitive-predictors-in-progressive-ms-preliminary-evidence
#16
Adam Gerstenecker, Kathleen Lowry, Terina Myers, Khurram Bashir, Kristen L Triebel, Roy C Martin, Daniel C Marson
BACKGROUND: Medical decision-making capacity (MDC) refers to the ability to make informed decisions about treatment and declines in cognition are associated with declines in MDC across multiple disease entities. However, although it is well known that cognitive impairment is prevalent in multiple sclerosis (MS), little is known about MDC in the disease. METHODS: Data from 22 persons with progressive MS and 18 healthy controls were analyzed. All diagnoses were made by a board-certified neurologist with experience in MS...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28861122/the-role-of-natalizumab-in-the-treatment-of-multiple-sclerosis-benefits-and-risks
#17
REVIEW
Barry A Singer
Natalizumab, a monoclonal antibody that blocks lymphocyte infiltration in the central nervous system, is a valuable tool in the treatment of relapsing forms of multiple sclerosis (MS). In a phase III clinical trial comparing natalizumab with placebo over 2 years, natalizumab reduced annualized relapse rate by 68%, 12-week confirmed disability progression by 42%, and reduced contrast-enhancing lesions by 92%. In post hoc analyses, natalizumab treatment was associated with 37% of patients achieving no evidence of disease activity (versus 7% on placebo) and 30% achieving sustained disability improvement (versus 19% on placebo)...
September 2017: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/28858531/an-update-on-cladribine-for-relapsing-remitting-multiple-sclerosis
#18
Trygve Holmøy, Øivind Torkildsen, Kjell-Morten Myhr
Despite recent progress, currently available therapies for relapsing remitting multiple sclerosis (MS) are only partly effective, and their use is limited by tolerability and safety issues, as well as high cost. Cladribine was originally rejected by the regulatory authorities in both the European Union and USA in 2011, but in June 2017 the European Medical Agency recommended marketing authorization for treatment of aggressive relapsing MS. Areas covered: We provide an update on chemistry, mechanism of action, efficacy and safety of cladribine for the treatment of MS...
September 11, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28857721/unexpected-additive-effects-of-minocycline-and-hydroxychloroquine-in-models-of-multiple-sclerosis-prospective-combination-treatment-for-progressive-disease
#19
Simon Faissner, Yasamin Mahjoub, Manoj Mishra, Steffen Haupeltshofer, Jennifer Nancy Hahn, Ralf Gold, Marcus Koch, Luanne M Metz, Tamir Ben-Hur, V Wee Yong
BACKGROUND: Most multiple sclerosis (MS) patients succumb to a progressive phenotype. Continued lymphocyte activity in the brain, microglia-mediated injury, iron deposition, and oxidative stress are characteristics of progressive MS. OBJECTIVE: As minocycline and hydroxychloroquine have been shown to inhibit microglia, we evaluated their effects on other outcomes relevant for progression. METHODS: Medications were evaluated in culture and in mice with acute and chronic experimental autoimmune encephalomyelitis (EAE)...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28856541/glycoprotein-nmb-an-emerging-role-in-neurodegenerative-disease
#20
REVIEW
Kevin M Budge, Matthew L Neal, Jason R Richardson, Fayez F Safadi
Neurodegeneration is characterized by severe neuronal loss leading to the cognitive and physical impairments that define various neurodegenerative diseases. Neuroinflammation is one hallmark of neurodegenerative diseases and can ultimately contribute to disease progression. Increased inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1β (IL-1 β), and tumor necrosis factor-α (TNF-α) are associated with Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS)...
August 30, 2017: Molecular Neurobiology
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