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https://www.readbyqxmd.com/read/27928949/from-leflunomide-to-teriflunomide-drug-development-and-immunosuppressive-oral-drugs-in-the-treatment-of-multiple-sclerosis
#1
Lilian Aly, Bernhard Hemmer, Thomas Korn
Immunosuppressive drugs have been used in the treatment of multiple sclerosis (MS) for a long time. Today, the increased number of approved substances and the possibility of an oral availability of some immunomodulators improve the therapeutic repertory and increase patient satisfaction and compliance. Teriflunomide is indicated as first line oral disease modifying therapy (DMT) in relapsing-remitting MS (RRMS). Its immunosuppressive capacity results from an inhibition of de novo pyrimidine synthesis in rapidly proliferating lymphocytes...
December 8, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27928430/optimal-treatment-of-tuberous-sclerosis-complex-associated-renal-angiomyolipomata-a-systematic-review
#2
REVIEW
John J Bissler, John C Kingswood
Renal angiomyolipomata associated with tuberous sclerosis complex are often bilateral, multiple and progressive. They cause significant morbidity and mortality in older children and adults. Surveillance and pre-emptive treatment reduce this risk. Recent research suggests treatment with mammalian target of rapamycin inhibitors is better at preventing bleeding, recurrence, and preserving renal function than percutaneous embolization.
August 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27927055/improving-the-therapeutic-efficacy-of-neural-progenitor-cell-transplantation-following-spinal-cord-injury
#3
Michael A Lane, Angelo C Lepore, Itzhak Fischer
There have been a wide range of preclinical studies testing cellular therapies to repair the injured spinal cord, yet they remain a challenge to translate because of inconsistencies in efficacy, difficulties in obtaining reliable and safe sources of donor cells, limited number of patients with acute/subacute SCI and the high costs of clinical trials. Area covered: This paper focusses on the therapeutic potential of neural precursor cells (NPCs) because they can provide the cellular components capable of promoting repair and enhancing functional improvement following spinal cord injury (SCI)...
December 7, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27924938/the-secretome-of-periodontal-ligament-stem-cells-from-ms-patients-protects-against-eae
#4
Thangavelu Soundara Rajan, Sabrina Giacoppo, Francesca Diomede, Patrizia Ballerini, Michele Paolantonio, Marco Marchisio, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
Manipulation of stem cells or stem cells-derived secretome has emerged as a novel alternative therapeutic option for multiple sclerosis (MS). Here we show that human periodontal ligament stem cells (hPDLSCs)-derived conditioned medium (hPDLSCs-CM) and purified exosomes/microvesicles (hPDLSCs-EMVs) obtained from Relapsing Remitting (RR)-MS patients and healthy donors block experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing anti-inflammatory and immunosuppressive effects in spinal cord and spleen, and reverse disease progression by restoring tissue integrity via remyelination in the spinal cord...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27923201/synthesis-and-biological-evaluation-of-a-new-class-of-benzothiazines-as-neuroprotective-agents
#5
Alessandra Mancini, Alessia Chelini, Angela Di Capua, Loretta Castelli, Simone Brogi, Marco Paolino, Germano Giuliani, Andrea Cappelli, Maria Frosini, Lorenzo Ricci, Erminia Leonelli, Gianluca Giorgi, Antonio Giordani, Jacopo Magistretti, Maurizio Anzini
Neurodegenerative diseases are disorders related to the degeneration of central neurons that gradually lead to various, severe alterations of cognitive and/or motor functions. Currently, for no such diseases does any pharmacological treatment exist able to arrest its progression. Riluzole (1) is a small molecule able to interfere with multiple cellular and molecular mechanisms of neurodegeneration, and is the only approved treatment of amyotrophic lateral sclerosis (ALS), the progression of which proved to significantly slow, thus increasing somewhat average survival...
November 27, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27921221/safety-and-efficacy-of-natalizumab-in-japanese-patients-with-relapsing-remitting-multiple-sclerosis-open-label-extension-study-of-a-phase-2-trial
#6
Takahiko Saida, Jun-Ichi Kira, Shuji Kishida, Takashi Yamamura, Nobuhisa Ohtsuka, Yan Ling, Shinichi Torii, Nisha Lucas, Geoffrey Kuesters, Deb Steiner, J T Tibung
INTRODUCTION: The efficacy of natalizumab was evaluated in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) in a 24-week, phase 2 bridging study. An open-label, 2-year extension study from this trial was conducted to assess the safety and efficacy of natalizumab treatment in Japanese patients. METHODS: A total of 97 patients (43 previously on placebo; 54 previously on natalizumab) who had completed the bridging study were treated with 300 mg natalizumab every 4 weeks...
December 5, 2016: Neurology and Therapy
https://www.readbyqxmd.com/read/27920149/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#7
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in posttranscriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter pathology. However, little is known about their role in grey matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27919507/predictors-of-long-term-interferon-discontinuation-in-newly-diagnosed-relapsing-multiple-sclerosis
#8
Marcello Moccia, Raffaele Palladino, Antonio Carotenuto, Cinzia Valeria Russo, Maria Triassi, Roberta Lanzillo, Vincenzo Brescia Morra
BACKGROUND: Interferon-β has long-term safety and efficacy profiles for Relapsing Remitting Multiple Sclerosis (RRMS). However, the increasing number of available treatments requires to improve patient profiling and to perform individualized clinical decisions. Therefore, the present study investigated predictors of Interferon-β discontinuation. METHODS: The present retrospective observational cohort study included 499 newly diagnosed, drug naïve RRMS subjects receiving Interferon-β as first disease modifying treatment (DMT), during a 7...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27919495/clinical-characteristics-of-patients-with-multiple-sclerosis-enrolled-in-a-new-registry-in-egypt
#9
Magd Zakaria, Dina A Zamzam, Mohamed A Abdel Hafeez, Mahmoud S Swelam, Shaimaa S Khater, Mai F Fahmy, Ayman Abdel Hady, Mohamed M Fouad, Azza Abdel Nasser, Hany Aref, Mohsen Gadallah
BACKGROUND: Epidemiological studies of multiple sclerosis (MS) are lacking in Egypt. OBJECTIVE: To study the characteristics of Egyptian patients with multiple sclerosis in a new registry in a major tertiary referral centre in Cairo, Egypt. SUBJECT AND METHODS: Patients were from the project MS database of the Multiple Sclerosis Unit at Ain Shams University Hospitals (N=950). We conducted a detailed medical history and examination including the Expanded Disability Status Scale (EDSS)...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27919489/cognitive-event-related-potentials-in-multiple-sclerosis-correlation-with-mri-and-neuropsychological-findings
#10
Vasilios K Kimiskidis, Vasileios Papaliagkas, Kyriaki Sotirakoglou, Zoi K Kouvatsou, Victoria K Kapina, Efrosini Papadaki, Vaia Tsimourtou, Elvira Masoura, Dimitrios A Kazis, Sotirios Papayiannopoulos, Triantafyllos Geroukis, Sevasti Bostanjopoulou
BACKGROUND: Cognitive event-related potentials (ERPs) have been previously correlated with T2 lesion load (Τ2LL) in patients with multiple sclerosis (MS). It is currently unknown, however, whether ERPs also correlate with brain atrophy or the presence of T1 hypointense lesions ("black holes") which reflect tissue destruction and axonal loss. The primary aim of the current study is to explore the effect of neuroradiological parameters such as brain atrophy, T1 and T2 lesion load on auditory ERPs in MS patients...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27919477/practice-effect-in-symbol-digit-modalities-test-in-multiple-sclerosis-patients-treated-with-natalizumab
#11
Malte Roar, Zsolt Illes, Tobias Sejbaek
OBJECTIVES: How practice effect influences cognitive testing measured by monthly Symbol Digit Modalities Test (SDMT) during natalizumab treatment, and what factors confound such effect. METHODS: Eighty patients were examined monthly with SDMT for 26.2±8.4 months. After 26.0±8.1 months, SDMT was also performed with a rearranged key in 59 cases. Results of SDMTs with the rearranged and previous regular key were compared. We examined if gender, age, Extended Disability Status Scale (EDSS), relapses, and disability progression/improvement influence SDMT performed with the regular and the rearranged key, respectively...
November 2016: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/27919195/efficacy-and-safety-of-mitoxantrone-use-in-primary-and-secondary-progressive-multiple-sclerosis-study-site-experience-based-on-the-therapy-of-104-patients
#12
Anetta Lasek-Bal, Karina Bartoszek, Arkadiusz Steposz, Przemyslaw Puz, Wieslaw Bal, Zofia Kazibutowska
Mitoxantrone (MX) is used in patients with primary and secondary progressive as well as relapsing-remitting type of multiple sclerosis (PPMS, SPMS, RRMS). The objective of our project was to evaluate the efficacy and safety of mitoxantrone use in patients with PPMS and SPMS. Methods The retrospective study included 104 patients (mean age 54.2 ± 9.0), with PPMS (13.46%) and SPMS (86.54%) treated with mitoxantrone. During single cycle of the MX therapy a dose of 12 mg/m2 of body surface area was administred and next cycles every three months up to a total dose of 140 mg/m2 were realized...
December 6, 2016: International Journal of Neuroscience
https://www.readbyqxmd.com/read/27918139/an-observational-study-to-assess-brain-mri-change-and-disease-progression-in-multiple-sclerosis-clinical-practice-the-ms-mrius-study
#13
Robert Zivadinov, Nasreen Khan, Jennie Medin, Pia Christoffersen, Jennifer Price, Jonathan R Korn, Ian Bonzani, Michael G Dwyer, Niels Bergsland, Ellen Carl, Diego Silva, Bianca Weinstock-Guttman
BACKGROUND & PURPOSE: To describe methodology, interim baseline, and longitudinal magnetic resonance imaging (MRI) acquisition parameter characteristics of the multiple sclerosis clinical outcome and MRI in the United States (MS-MRIUS). MATERIAL & METHODS: The MS-MRIUS is an ongoing longitudinal and retrospective study of MS patients on fingolimod. Clinical and brain MRI image scan data were collected from 600 patients across 33 MS centers in the United States. MRI brain outcomes included change in whole-brain volume, lateral ventricle volume, T2- and T1-lesion volumes, and new/enlarging T2 and gadolinium-enhancing lesions...
December 5, 2016: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/27917400/high-dose-biotin-treatment-for-secondary-progressive-multiple-sclerosis-may-interfere-with-thyroid-assays
#14
Alissa Minkovsky, Mark N Lee, Mitra Dowlatshahi, Trevor E Angell, Lilian S Mahrokhian, Athena K Petrides, Stacy E F Melanson, Ellen Marqusee, Whitney W Woodmansee
OBJECTIVE: To review cases and increase awareness in clinicians treating patients who may be taking biotin. METHODS: We describe the presentation and workup of a woman with secondary progressive multiple sclerosis on high dose biotin with laboratory studies suggestive of thyrotoxicosis. RESULTS: Plasma samples showed laboratory evidence of elevated thyroid hormone levels with elevated free thyroxine >7.8 ng/dl (reference interval (RI) 0...
2016: AACE Clin Case Rep
https://www.readbyqxmd.com/read/27914464/immunogenicity-of-human-interferon-beta-containing-pharmaceuticals
#15
V D Nazarov, S V Lapin, A V Mazing, E P Evdoshenko, A A Totolian
Multiple sclerosis is a severe autoimmune disease with inflammatory component that continues to be resistant to treatment. One of the approaches retarding its progression is based on using nonspecific therapy with human interferon-beta (IFN-β)-containing pharmaceuticals. Neutralizing antibodies (NAbs) against genetically engineered pharmaceuticals developed by the patient's immune system, which reduce their therapeutic and biological activity, pose a serious problem. Cell lines sensitive to IFN-β activity also quantifying NAb level are applied because direct measurement of IFN-β antiviral activity is complicated...
November 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/27913115/computer-design-synthesis-and-bioactivity-analyses-of-drugs-like-fingolimod-used-in-the-treatment-of-multiple-sclerosis
#16
Gurbet Çelik Turgut, Doğukan Doyduk, Yılmaz Yıldırır, Serkan Yavuz, Atilla Akdemir, Ali Dişli, Alaattin Şen
Multiple sclerosis (MS) is a very common disease of vital importance. In the MS treatment, some drugs such as fingolimod which help to protect nerves from damage are used. The main goal of the drug therapy in MS is to take control of the inflammation which leads to the destruction of myelin and axons in nerve cell and thus prevent and stop the progression of the disease. Fingolimod (FTY720) is an orally active immunomodulatory drug that has been used for the treatment of relapsing-remitting multiple sclerosis...
November 18, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27912762/regulation-of-effector-function-of-cns-autoreactive-cd4-t-cells-through-inhibitory-receptors-and-il-7r%C3%AE
#17
Patrick K Nuro-Gyina, Elizabeth L Rieser, Marissa C Granitto, Wei Pei, Yue Liu, Priscilla W Lee, Saba Aqel, Jian Zhang, Amy E Lovett-Racke, Michael K Racke, Yuhong Yang
BACKGROUND: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by inflammation, demyelination, and neuronal degeneration, where myelin-specific CD4 T cells play critical roles in the formation of acute MS lesions and disease progression. The suppression of IL-7Rα expression and the upregulation of inhibitory receptors (PD-1, etc.) are essential parts of the cell-intrinsic immunosuppressive program regulating T effector functions to prevent autoimmunity. However, little is known on the factors regulating IL-7Rα/PD-1 balance in myelin-specific CD4 T effector/memory cells during the development of CNS autoimmunity...
December 3, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27911409/measuring-progressive-neurological-disability-in-a-mouse-model-of-multiple-sclerosis
#18
Francesca Gilli, Darlene B Royce, Andrew R Pachner
After intracerebral infection with the Theiler's Murine Encephalomyelitis Virus (TMEV), susceptible SJL mice develop a chronic-progressive demyelinating disease, with clinical features similar to the progressive forms of multiple sclerosis (MS). The mice show progressive disability with loss of motor and sensory functions, which can be assessed with multiple apparatuses and protocols. Among them, the Rotarod performance test is a very common behavioral test, its advantage being that it provides objective measurements, but it is often used assuming that it is straightforward and simple...
November 14, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910985/uvb-radiation-vitamin-d-and-multiple-sclerosis
#19
H F DeLuca, L Plum
Acheson et al. (1960) observed an inverse relationship between sunlight exposure and the incidence of Multiple Sclerosis (MS). This led to the suggestion that increased levels of vitamin D caused by sunlight in some way suppresses MS. Further, super physiological doses of the metabolically active metabolite of vitamin D, i.e. 1α,25 dihydroxy vitamin D suppresses the animal model of MS i.e. experimental autoimmune encephalomyelitis (EAE). However, this response was accompanied by hypercalcemia. Hypercalcemia itself can suppress EAE...
December 2, 2016: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/27908171/automated-detection-of-white-matter-hyperintensities-of-all-sizes-in-cerebral-small-vessel-disease
#20
Mohsen Ghafoorian, Nico Karssemeijer, Inge W M van Uden, Frank-Erik de Leeuw, Tom Heskes, Elena Marchiori, Bram Platel
PURPOSE: White matter hyperintensities (WMH) are seen on FLAIR-MRI in several neurological disorders, including multiple sclerosis, dementia, Parkinsonism, stroke and cerebral small vessel disease (SVD). WMHs are often used as biomarkers for prognosis or disease progression in these diseases, and additionally longitudinal quantification of WMHs is used to evaluate therapeutic strategies. Human readers show considerable disagreement and inconsistency on detection of small lesions. A multitude of automated detection algorithms for WMHs exists, but since most of the current automated approaches are tuned to optimize segmentation performance according to Jaccard or Dice scores, smaller WMHs often go undetected in these approaches...
December 2016: Medical Physics
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