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Progressive multiple sclerosis treatment

Zimu Zhang, Zhenyi Xue, Ying Liu, Hongkun Liu, Xiangdong Guo, Yan Li, Hongwei Yang, Lijuan Zhang, Yurong Da, Zhi Yao, Rongxin Zhang
Among T helper (Th) cell subsets differentiated from naive CD4+ T cells, IL-17-producing Th17 cells are closely associated with the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and the MS animal model, experimental autoimmune encephalomyelitis (EAE). The modulation of Th17 differentiation offers a potential avenue for treatment. Although a series of microRNAs (miRNAs) that modulate autoimmune disease development have been reported, further studies on miRNA roles in Th17 differentiation and MS pathogenesis are still warranted...
March 12, 2018: Brain, Behavior, and Immunity
Raju Kapoor, Pei-Ran Ho, Nolan Campbell, Ih Chang, Aaron Deykin, Fiona Forrestal, Nisha Lucas, Bei Yu, Douglas L Arnold, Mark S Freedman, Myla D Goldman, Hans-Peter Hartung, Eva Kubala Havrdová, Douglas Jeffery, Aaron Miller, Finn Sellebjerg, Diego Cadavid, Dan Mikol, Deborah Steiner
BACKGROUND: Although several disease-modifying treatments are available for relapsing multiple sclerosis, treatment effects have been more modest in progressive multiple sclerosis and have been observed particularly in actively relapsing subgroups or those with lesion activity on imaging. We sought to assess whether natalizumab slows disease progression in secondary progressive multiple sclerosis, independent of relapses. METHODS: ASCEND was a phase 3, randomised, double-blind, placebo-controlled trial (part 1) with an optional 2 year open-label extension (part 2)...
March 12, 2018: Lancet Neurology
Peter Göttle, Anastasia Manousi, David Kremer, Laura Reiche, Hans-Peter Hartung, Patrick Küry
BACKGROUND: Multiple sclerosis (MS) is a neuroinflammatory autoimmune disease of the central nervous system (CNS) which in most cases initially presents with episodes of transient functional deficits (relapsing-remitting MS; RRMS) and eventually develops into a secondary progressive form (SPMS). Aside from neuroimmunological activities, MS is also characterized by neurodegenerative and regenerative processes. The latter involve the restoration of myelin sheaths-electrically insulating structures which are the primary targets of autoimmune attacks...
March 13, 2018: Journal of Neuroinflammation
Annie C Bowles, Rachel M Wise, Brittany Y Gerstein, Robert C Thomas, Roberto Ogelman, Regan C Manayan, Bruce A Bunnell
BACKGROUND: The therapeutic efficacy of adipose-derived stem cells (ASCs) has been investigated for numerous clinical indications, including autoimmune and neurodegenerative diseases. Less is known using the crude adipose product called stromal vascular fraction (SVF) as therapy, although our previous studies demonstrated greater efficacy at late-stage disease compared to ASCs in the experimental autoimmune encephalomyelitis (EAE) mouse, a model of multiple sclerosis. In this study, SVF cells and ASCs were administered during the pathogenic progression, designated as early disease, to elucidate immunomodulatory mechanisms when high immune cell activities associated with autoimmune signaling occur...
March 13, 2018: Journal of Neuroinflammation
Shinji Aoyama, Masahiro Mori, Akiyuki Uzawa, Tomohiko Uchida, Hiroki Masuda, Ryohei Ohtani, Satoshi Kuwabara
BACKGROUND: The risk of developing progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis (MS) patients is related to serum anti-JCV antibody (JCVAb) index. However, the correlation of JCVAb index with other disease-modifying treatments (DMTs) is not well understood. OBJECTIVE: In this study, we investigated the JCVAb seropositivity rate/JCVAb indexes and its correlation with clinical profiles in Japanese MS patients, and the relationship between JCVAb indexes and DMTs...
March 12, 2018: Journal of Neurology
Martijn T Wijburg, Iris Kleerekooper, Birgit I Lissenberg-Witte, Marlieke de Vos, Clemens Warnke, Bernard M J Uitdehaag, Frederik Barkhof, Joep Killestein, Mike P Wattjes
Importance: The JC virus (JCV) was named after the first patient to be described with progressive multifocal leukoencephalopathy (PML), John Cunningham. Detection of JC virus DNA in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), and of specific lesions by brain magnetic resonance imaging (MRI), are both considered essential for the diagnosis of natalizumab-associated PML (NTZ-PML) in patients with multiple sclerosis. However, strict pharmacovigilance by MRI can result in detection of patients with small lesions and undetectable JCV DNA in CSF...
March 12, 2018: JAMA Neurology
Paul A Smith, Cindy Schmid, Stefan Zurbruegg, Magali Jivkov, Arno Doelemeyer, Diethilde Theil, Valérie Dubost, Nicolau Beckmann
Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7 Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain...
March 3, 2018: Journal of Neuroimmunology
L Monge Galindo, A L Martínez de Morentín, V Pueyo Royo, J P García Iñiguez, S Sánchez Marco, J López-Pisón, J L Peña-Segura
INTRODUCTION AND OBJECTIVE: In this article, we present our experience on optic neuritis (ON) and provide a diagnostic/therapeutic protocol, intended to rule out other aetiologies (particularly infection), and a fact sheet for parents. MATERIAL AND METHODS: We conducted a descriptive, retrospective study of patients with ON over a 27-year period (1990-2017). A review of the available scientific evidence was performed in order to draft the protocol and fact sheet...
March 8, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
Neil H Riordan, Isabela Morales, Giselle Fernández, Nicole Allen, Neal E Fearnot, Michael E Leckrone, Dedra Jones Markovich, Darla Mansfield, Dorita Avila, Amit N Patel, Santosh Kesari, Jorge Paz Rodriguez
BACKGROUND: Multiple sclerosis (MS) is a progressively debilitating neurological condition in which the immune system abnormally erodes the myelin sheath insulating the nerves. Mesenchymal stem cells (MSC) have been used in the last decade to safely treat certain immune and inflammatory conditions. METHODS: A safety and feasibility study was completed on the use of umbilical cord MSC (UCMSC) as a treatment for MS. In this 1-year study, consenting subjects received seven intravenous infusions of 20 × 106 UCMSC over 7 days...
March 9, 2018: Journal of Translational Medicine
Toru Koda, Akiko Namba, Yuji Nakatsuji, Masaaki Niino, Yusei Miyazaki, Tomoyuki Sugimoto, Makoto Kinoshita, Kazushiro Takata, Kazuya Yamashita, Mikito Shimizu, Toshiyuki Fukazawa, Atsushi Kumanogoh, Hideki Mochizuki, Tatsusada Okuno
We previously demonstrated that patients with multiple sclerosis (MS) of high serum Sema4A levels are resistant to IFN-β therapy. To further elucidate the role of serum Sema4A as a biomarker for therapeutic stratification in MS patients, it is important to clarify the efficacy of other disease-modifying drugs (DMD) in those with high serum Sema4A levels. Thus, in this study we investigated whether fingolimod has beneficial effects on MS patients with high Sema4A levels. We retrospectively analyzed annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) change in 56 relapsing-remitting multiple sclerosis (RRMS) patients who had been treated with fingolimod, including those who switched from IFN-β therapy...
2018: PloS One
Ester Canto, Noriko Isobe, Alessandro Didonna, Stephen L Hauser, Jorge R Oksenberg
BACKGROUND: Multiple sclerosis (MS) is characterized by increased activation of peripheral blood mononuclear cells (PBMCs), linked to perturbations in the phosphorylation of signaling proteins. METHODS: We developed a phosphoflow cytometry protocol to assess the levels of 11 phosphorylated nuclear proteins at baseline conditions and after cell activation in distinct PBMC populations from 41 treatment-naïve relapsing-remitting (RR) MS subjects and 37 healthy controls, and in a second cohort of 9 untreated RRMS patients and 10 secondary progressive (SP) MS patients...
March 7, 2018: Journal of Neuroinflammation
Michael Dietrich, Niklas Helling, Alexander Hilla, Annemarie Heskamp, Andrea Issberner, Thomas Hildebrandt, Zippora Kohne, Patrick Küry, Carsten Berndt, Orhan Aktas, Dietmar Fischer, Hans-Peter Hartung, Philipp Albrecht
BACKGROUND: In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also beneficial in the early, more inflammatory-driven phases. As clinical studies are costly and time consuming, optic neuritis (ON) is often used for investigating neuroprotective or regenerative therapeutics...
March 7, 2018: Journal of Neuroinflammation
Neepa Patel, Hannah Combs, Michele York, Cecile Phan, Joohi Jimenez-Shahed
Pseudobulbar affect (PBA) is a syndrome of affective disturbance associated with inappropriate laughter and crying, independent of mood. PBA is common in amyotrophic lateral sclerosis (ALS) and increasingly recognized in Parkinson's disease (PD) and atypical parkinsonism (aP). Correlates of PBA have not been systematically studied. The purpose of this study was to determine whether cognitive and psychiatric comorbidities correlated with patient-reported symptoms of PBA by using the Center for Neurological Study-Lability Scale among patients with ALS, PD, and aP...
March 5, 2018: Journal of Neuropsychiatry and Clinical Neurosciences
Woo Suk Tae, Byung Joo Ham, Sung Bom Pyun, Shin Hyuk Kang, Byung Jo Kim
Diffusion-tensor imaging (DTI) is a noninvasive medical imaging tool used to investigate the structure of white matter. The signal contrast in DTI is generated by differences in the Brownian motion of the water molecules in brain tissue. Postprocessed DTI scalars can be used to evaluate changes in the brain tissue caused by disease, disease progression, and treatment responses, which has led to an enormous amount of interest in DTI in clinical research. This review article provides insights into DTI scalars and the biological background of DTI as a relatively new neuroimaging modality...
February 28, 2018: Journal of Clinical Neurology
Sherif M Hamdy, Maged Abdel-Naseer, Nevin M Shalaby, Alaa Elmazny, Marian Girgis, Mona A Nada, Amr Hassan, Husam S Mourad, Mohamed I Hegazy, Ahmed Abdelalim, Nirmeen A Kishk, Noha T Abokrysha, Shaimaa A Genedy, Ehab A Essawy, Hatem S Shehata
Introduction: Although the frequency of pediatric-onset multiple sclerosis (POMS) has increased in recent decades, it is still highly uncommon, which creates a need for the involvement of more registries from various clinical centers. Objective: To characterize the demographic, clinical, and paraclinical features of Egyptian patients with POMS. Patients and methods: A retrospective chart review study was undertaken on 237 Egyptian patients with demyelinating events which started before the age of 18 years who attended one of five tertiary referral centers in Cairo, Egypt...
2018: Neuropsychiatric Disease and Treatment
Reza Lasemi, Michael Kundi, Nahid Beladi Moghadam, Hanns Moshammer, Johannes A Hainfellner
BACKGROUND: Vitamin K2 (VK2) belongs to the vitamin K family and comprises a number of subtypes differing in length of side chains consisting of isoprenoid groups (menaquinone-n, MK-n). It is essential for a number of physiological functions although the full spectrum of activity has not yet been elucidated. Due to its role in protection of mitochondrial damage, VK2 could be relevant in preventing disease progress in multiple sclerosis (MS). METHODS: We measured VK2 serum levels by the double antibody sandwich Enzyme-linked Immunosorbent Assay (ELISA) technique in MS patients and age and sex matched controls, both under vitamin D supplementation, and related it to disease characteristics and treatment...
March 2, 2018: Wiener Klinische Wochenschrift
Anu Paul, Manuel Comabella, Roopali Gandhi
Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease with a complex clinical course characterized by inflammation, demyelination, and axonal degeneration. Diagnosis of MS most commonly includes finding lesions in at least two separate areas of the central nervous system (CNS), including the brain, spinal cord, and optic nerves. In recent years, there has been a remarkable increase in the number of available treatments for MS. An optimal treatment is usually based on a personalized approach determined by an individual patient's prognosis and treatment risks...
March 2, 2018: Cold Spring Harbor Perspectives in Medicine
Majid Ghareghani, Kazem Zibara, Hossein Sadeghi, Naser Farhadi
Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease in the central nervous system (CNS). Melatonin is an effective treatment in MS patients and experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Melatonin secretion peaks at 2 AM, concomitant with the time at which the muscles are resting and the body is exerting its antioxidant activity. The current study was designed to investigate combination treatment of baclofen, a muscle relaxant drug, and melatonin in EAE mice...
March 1, 2018: Cellular and Molecular Neurobiology
Marta Kinga Lemieszek, Andrzej Stepulak, Katarzyna Sawa-Wejksza, Arkadiusz Czerwonka, Chrysanthy Ikonomidou, Wojciech Rzeski
Regardless of contemporary improvements in cancer treatment, the results of drug treatment are not always efficacious. Thus, the development of novel approaches that affect cancer cell-specific metabolic pathways are needed. Since much evidence has shown that tumor cell proliferation and motility are stimulated by glutamate via activation of its receptors, use of antagonists to these receptors may be the key to control cancer cell progression. Riluzole noncompetitive metabotropic glutamate receptor 1 (mGluR1) antagonist, commonly used to treat patients with amyotrophic lateral sclerosis (ALS), has shown some antineoplastic properties against melanoma, breast and prostate cancer...
February 28, 2018: Anti-cancer Agents in Medicinal Chemistry
Santa Mammana, Placido Bramanti, Emanuela Mazzon, Eugenio Cavalli, Maria Sofia Basile, Paolo Fagone, Maria Cristina Petralia, James Andrew McCubrey, Ferdinando Nicoletti, Katia Mangano
The PI3K/AKT/mTOR pathway is an intracellular signalling pathway that regulates cell activation. proliferation, metabolism and apoptosis. Increasing body of data suggests that alterations in the PI3K/AKT/mTOR pathway may result in an enhanced susceptibility to autoimmunity. Multiple Sclerosis (MS) is one of the most common chronic inflammatory diseases of the central nervous system leading to demyelination and neurodegeneration. In the current study, we have firstly evaluated in silico the involvement of the mTOR network on the generation and progression of MS and on oligodendrocyte function, making use of currently available whole-genome transcriptomic data...
February 2, 2018: Oncotarget
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