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Progressive multiple sclerosis treatment

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https://www.readbyqxmd.com/read/28812220/sphingosine-1-phosphate-receptor-modulators-for-the-treatment-of-multiple-sclerosis
#1
REVIEW
Burhan Z Chaudhry, Jeffrey A Cohen, Devon S Conway
Sphingosine 1-phosphate receptor (S1PR) modulators possess a unique mechanism of action in the treatment of multiple sclerosis (MS). Subtype 1 of the S1PR is expressed on the surface of lymphocytes and is important in regulating egression from lymph nodes. The S1PR modulators indirectly antagonize the receptor's function leading to sequestration of lymphocytes in the lymph nodes. Fingolimod was the first S1PR modulator to receive regulatory approval for relapsing-remitting MS after 2 phase III trials demonstrated potent efficacy, safety, and tolerability...
August 15, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28808113/lncrna-gas5-inhibits-microglial-m2-polarization-and-exacerbates-demyelination
#2
Dingya Sun, Zhongwang Yu, Xue Fang, Mingdong Liu, Yingyan Pu, Qi Shao, Dan Wang, Xiaolin Zhao, Aijun Huang, Zhenghua Xiang, Chao Zhao, Robin Jm Franklin, Li Cao, Cheng He
The regulation of inflammation is pivotal for preventing the development or reoccurrence of multiple sclerosis (MS). A biased ratio of high-M1 versus low-M2 polarized microglia is a major pathological feature of MS Here, using microarray screening, we identify the long noncoding RNA (lncRNA) GAS5 as an epigenetic regulator of microglial polarization. Gain- and loss-of-function studies reveal that GAS5 suppresses microglial M2 polarization. Interference with GAS5 in transplanted microglia attenuates the progression of experimental autoimmune encephalomyelitis (EAE) and promotes remyelination in a lysolecithin-induced demyelination model...
August 14, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28806143/whose-preferences-matter-a-patient-centered-approach-for-eliciting-treatment-goals
#3
Nananda F Col, Andrew J Solomon, Vicky Springmann, Calvin P Garbin, Carolina Ionete, Lori Pbert, Enrique Alvarez, Brenda Tierman, Ashli Hopson, Christen Kutz, Idanis Berrios Morales, Carolyn Griffin, Glenn Phillips, Long H Ngo
BACKGROUND: Patients facing a high-stakes clinical decision are often confronted with an overwhelming array of options. High-quality decisions about treatment should reflect patients' preferences as well as their clinical characteristics. Preference-assessment instruments typically focus on pre-selected clinical outcomes and attributes chosen by the investigator. OBJECTIVE: We sought to develop a patient-centered approach to elicit and compare the treatment goals of patients with multiple sclerosis (MS) and healthcare providers (HCPs)...
August 1, 2017: Medical Decision Making: An International Journal of the Society for Medical Decision Making
https://www.readbyqxmd.com/read/28805578/nonmotor-symptoms-in-amyotrophic-lateral-sclerosis-a-systematic-review
#4
Ton Fang, Felix Jozsa, Ammar Al-Chalabi
BACKGROUND: ALS is a progressive neurodegenerative disease with no curative treatment. Nonmotor symptoms presenting in ALS may cause significant distress, worsen prognosis, and affect survival. OBJECTIVE: To systematically review evidence for the prevalence of nonmotor ALS symptoms, and treatment options. METHODS: Multiple medical literature databases were searched and studies screened using predefined inclusion criteria. Of 4580 studies, 44 were eligible for inclusion with 25 relating to treatment and 19 to the prevalence of nonmotor symptoms in ALS...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28794248/anti-inflammatory-disease-modifying-treatment-and-short-term-disability-progression-in-spms
#5
Johannes Lorscheider, Vilija G Jokubaitis, Tim Spelman, Guillermo Izquierdo, Alessandra Lugaresi, Eva Havrdova, Dana Horakova, Maria Trojano, Pierre Duquette, Marc Girard, Alexandre Prat, François Grand'Maison, Pierre Grammond, Eugenio Pucci, Cavit Boz, Patrizia Sola, Diana Ferraro, Daniele Spitaleri, Jeanette Lechner-Scott, Murat Terzi, Vincent Van Pesch, Gerardo Iuliano, Roberto Bergamaschi, Cristina Ramo-Tello, Franco Granella, Celia Oreja-Guevara, Helmut Butzkueven, Tomas Kalincik
OBJECTIVE: To investigate the effect of disease-modifying treatment on short-term disability outcomes in secondary progressive multiple sclerosis (SPMS). METHODS: Using MSBase, an international cohort study, we previously validated a highly accurate definition of SPMS. Here, we identified patients in MSBase who were either untreated or treated with a disease-modifying drug when meeting this definition. Propensity score matching was used to select subpopulations with comparable baseline characteristics...
August 9, 2017: Neurology
https://www.readbyqxmd.com/read/28793364/melatonin-reduces-inflammatory-response-in-peripheral-t-helper-lymphocytes-from-relapsing-remitting-multiple-sclerosis-patients
#6
Nuria Álvarez-Sánchez, Ivan Cruz-Chamorro, María Díaz-Sánchez, Helia Sarmiento-Soto, Pablo Medrano-Campillo, Alicia Martínez-López, Patricia Judith Lardone, Juan Miguel Guerrero, Antonio Carrillo-Vico
Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system in which the immune system plays a central role. In particular, effector populations such as T helper (Th) 1, Th9, Th17 and Th22 cells are involved in disease development, whereas T regulatory cells (Tregs) are associated with the resolution of the disease. Melatonin levels are impaired in MS patients, and exogenous melatonin ameliorates the disease in MS animal models by modulating the Th1/Th17/Treg responses and also improves quality of life and several symptoms in MS patients...
August 9, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28792504/common-gene-network-signature-of-different-neurological-disorders-and-their-potential-implications-to-neuroaids
#7
Vidya Sagar, S Pilakka-Kanthikeel, Paola C Martinez, V S R Atluri, M Nair
The neurological complications of AIDS (neuroAIDS) during the infection of human immunodeficiency virus (HIV) are symptomized by non-specific, multifaceted neurological conditions and therefore, defining a specific diagnosis/treatment mechanism(s) for this neuro-complexity at the molecular level remains elusive. Using an in silico based integrated gene network analysis we discovered that HIV infection shares convergent gene networks with each of twelve neurological disorders selected in this study. Importantly, a common gene network was identified among HIV infection, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and age macular degeneration...
2017: PloS One
https://www.readbyqxmd.com/read/28791401/implications-of-white-matter-damage-in-amyotrophic-lateral-sclerosis-review
#8
Ting Zhou, Tina Khorshid Ahmad, Kiana Gozda, Jessica Truong, Jiming Kong, Michael Namaka
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronal‑glial interactions...
August 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28780745/effectiveness-and-safety-of-dimethyl-fumurate-treatment-in-relapsing-multiple-sclerosis-patients-a-real-world-evidence
#9
Raed Alroughani, Samar Farouk Ahmed, Raed Behbehani, Jasem Al-Hashel
INTRODUCTION: Dimethyl fumurate (DMF) has been recently approved as a disease-modifying therapy for the treatment of multiple sclerosis (MS). Post-marketing studies are important to confirm what was established in clinical trials. OBJECTIVE: To evaluate effectiveness and safety of DMF and to measure the occurrence of lymphopenia in a cohort of MS patients in a clinical setting. METHODS: Using the national MS registry, we prospectively assessed relapsing MS patients who had been prescribed DMF for at least 6 months...
August 5, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#10
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28770481/the-role-of-advanced-magnetic-resonance-imaging-techniques-in-multiple-sclerosis-clinical-trials
#11
REVIEW
Kedar R Mahajan, Daniel Ontaneda
Magnetic resonance imaging has been crucial in the development of anti-inflammatory disease-modifying treatments. The current landscape of multiple sclerosis clinical trials is currently expanding to include testing not only of anti-inflammatory agents, but also neuroprotective, remyelinating, neuromodulating, and restorative therapies. This is especially true of therapies targeting progressive forms of the disease where neurodegeneration is a prominent feature. Imaging techniques of the brain and spinal cord have rapidly evolved in the last decade to permit in vivo characterization of tissue microstructural changes, connectivity, metabolic changes, neuronal loss, glial activity, and demyelination...
August 2, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28770420/efficacy-and-tolerability-of-delayed-release-dimethyl-fumarate-in-black-hispanic-and-asian-patients-with-relapsing-remitting-multiple-sclerosis-post-hoc-integrated-analysis-of-define-and-confirm
#12
Robert J Fox, Ralf Gold, J Theodore Phillips, Macaulay Okwuokenye, Annie Zhang, Jing L Marantz
INTRODUCTION: Clinical course and treatment response may vary according to race/ethnicity in multiple sclerosis (MS) patients. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated significant efficacy and a favorable benefit-risk profile in relapsing-remitting MS (RRMS) patients in the 2-year phase III DEFINE/CONFIRM studies. METHODS: In this post hoc analysis of integrated data from DEFINE/CONFIRM, we assessed clinical efficacy and safety/tolerability in black, Hispanic, and Asian patients treated with DMF 240 mg twice daily (approved dosage) or placebo...
August 2, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28770099/balance-right-in-multiple-sclerosis-brims-a-guided-self-management-programme-to-reduce-falls-and-improve-quality-of-life-balance-and-mobility-in-people-with-secondary-progressive-multiple-sclerosis-a-protocol-for-a-feasibility-randomised-controlled-trial
#13
H Gunn, J Andrade, L Paul, L Miller, S Creanor, C Green, J Marsden, P Ewings, M Berrow, J Vickery, A Barton, B Marshall, J Zajicek, J A Freeman
BACKGROUND: Impaired mobility is a cardinal feature of multiple sclerosis (MS) and is rated by people with MS as their highest priority. By the secondary progressive phase, balance, mobility and physical activity levels are significantly compromised; an estimated 70% of people with secondary progressive MS fall regularly. Our ongoing research has systematically developed 'Balance Right in MS' (BRiMS), an innovative, manualised 13-week guided self-management programme tailored to the needs of people with MS, designed to improve safe mobility and minimise falls...
2018: Pilot and Feasibility Studies
https://www.readbyqxmd.com/read/28766982/serum-met-5-enkephalin-levels-are-reduced-in-multiple-sclerosis-and-restored-by-low-dose-naltrexone
#14
Michael D Ludwig, Ian S Zagon, Patricia J McLaughlin
Low-dose naltrexone is a widely used off-label therapeutic prescribed for a variety of immune-related disorders. The mechanism underlying low-dose naltrexone's efficacy for fatigue, Crohn's disease, fibromyalgia, and multiple sclerosis is, in part, intermittent blockade of opioid receptors followed by upregulation of endogenous opioids. Short, intermittent blockade by naltrexone specifically blocks the opioid growth factor receptor resulting in biofeedback events that increase production of the endogenous opioid growth factor (OGF) (chemically termed [Met(5)]-enkephalin) facilitating interactions between opioid growth factor and opioid growth factor receptor that ultimately, result in inhibited cell proliferation...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28762877/rituximab-in-multiple-sclerosis-frequency-and-clinical-relevance-of-anti-drug-antibodies
#15
Nicky Dunn, Alexander Juto, Malin Ryner, Ali Manouchehrinia, Luca Piccoli, Katharina Fink, Fredrik Piehl, Anna Fogdell-Hahn
BACKGROUND: Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown. OBJECTIVE: To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients. METHODS: Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion...
July 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28758631/statins-are-ineffective-at-reducing-neuroinflammation-or-prolonging-survival-in-scrapie-infected-mice
#16
James A Carroll, Brent Race, Katie Phillips, James F Striebel, Bruce Chesebro
Neuroinflammation is a prominent component of several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, tauopathies, amyotrophic lateral sclerosis and prion diseases. In such conditions, the ability to decrease neuroinflammation by drug therapy may influence disease progression. Statins have been used to treat hyperlipidemia as well as reduce neuroinflammation and oxidative stress in various tissues. In previous studies, treatment of scrapie-infected mice with the type 1 statins, simvastatin or pravastatin, showed a small beneficial effect on survival time...
July 31, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28754822/epigenetic-research-in-multiple-sclerosis-progress-challenges-and-opportunities
#17
Galina Zheleznyakova, Eliane Piket, Francesco Marabita, Majid Pahlevan Kakhki, Ewoud Ewing, Sabrina Ruhrmann, Maria Needhamsen, Maja Jagodic, Lara Kular
Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. MS likely results from a complex interplay between predisposing causal gene variants (the strongest influence coming from HLA class II locus) and environmental risk factors such as smoking, infectious mononucleosis and lack of sun exposure/vitamin D. However, little is known about the mechanisms underlying MS development and progression. Moreover, the clinical heterogeneity and variable response to treatment represent additional challenges to a comprehensive understanding and efficient treatment of disease...
July 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28752856/multiple-sclerosis-treatment-of-cognitive-impairment-in-secondary-progressive-ms
#18
Anthony Feinstein
No abstract text is available yet for this article.
July 28, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28751457/2-arachidonoylglycerol-reduces-proteoglycans-and-enhances-remyelination-in-a-progressive-model-of-demyelination
#19
A Feliu, Bonilla I Del Río, F J Carrillo-Salinas, G Hernández-Torres, L Mestre, N Puente, S Ortega-Gutiérrez, M L López-Rodríguez, P Grandes, M Mecha, C Guaza
The failure to undergo remyelination is a critical impediment to recovery in multiple sclerosis (MS). Chondroitin sulfate proteoglycans (CSPGs) accumulate at demyelinating lesions creating a non-permissive environment that impairs axon regeneration and remyelination. Here, we reveal a new role for 2-arachinonoylglycerol (2-AG), the major CNS endocannabinoid, in the modulation of CSPG deposition in a progressive model of MS, the Theiler's murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD)...
July 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28744286/a-b-cell-driven-autoimmune-pathway-leading-to-pathological-hallmarks-of-progressive-multiple-sclerosis-in-the-marmoset-experimental-autoimmune-encephalomyelitis-model
#20
REVIEW
Bert A 't Hart, Jordon Dunham, Bart W Faber, Jon D Laman, Jack van Horssen, Jan Bauer, Yolanda S Kap
The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34-56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund's adjuvant (IFA)]...
2017: Frontiers in Immunology
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