Amelia Nathania Dong, Boon Hooi Tan, Yan Pan, Chin Eng Ong
Since the discovery of its role in vitamin D metabolism, significant progress has been made in the understanding of gene organisation, protein structure, catalytic function, and genetic polymorphism of cytochrome P450 2R1 (CYP2R1). Located on chromosome 11p15.2, CYP2R1 possesses five exons, unlike most other CYP isoforms that carry nine exons. CYP2R1 crystal structure displays a fold pattern typical of a CYP protein, with 12 a-helices as its structural core, and b-sheets mostly arranged on one side, and the heme buried in the interior part of the protein...
2021: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Yuri Ahuja, Nicole Kim, Liang Liang, Tianrun Cai, Kumar Dahal, Thany Seyok, Chen Lin, Sean Finan, Katherine Liao, Guergana Savovoa, Tanuja Chitnis, Tianxi Cai, Zongqi Xia
OBJECTIVE: No relapse risk prediction tool is currently available to guide treatment selection for multiple sclerosis (MS). Leveraging electronic health record (EHR) data readily available at the point of care, we developed a clinical tool for predicting MS relapse risk. METHODS: Using data from a clinic-based research registry and linked EHR system between 2006 and 2016, we developed models predicting relapse events from the registry in a training set (n = 1435) and tested the model performance in an independent validation set of MS patients (n = 186)...
February 24, 2021: Annals of Clinical and Translational Neurology
Christina Zhukovsky, Stephanie Herman, Anna Wiberg, Janet L Cunningham, Kim Kultima, Joachim Burman
OBJECTIVE: To identify serum proteins associated with MS and affected by interferon beta treatment. METHODS: Plasma samples from 29 untreated relapsing-remitting MS patients and 15 healthy controls were investigated with a multiplexed panel containing 92 proteins related to inflammation. Follow-up samples were available from 13 patients at 1 and 3 months after initiation of treatment with interferon beta-1a. RESULTS: Ten proteins were differentially expressed in MS patients...
February 24, 2021: Acta Neurologica Scandinavica
Lorenza Angelini, Ellen Buckley, Tecla Bonci, Alexandra Radford, Basil Sharrack, David Paling, Krishnan Padmakumari Sivaraman Nair, Claudia Mazza
OBJECTIVE: Mobility assessment is critical in the clinical management of people with Multiple Sclerosis (pwMS). Instrumented gait analysis provides a plethora of metrics for quantifying concurrent factors contributing to gait deterioration. However, a gait model discriminating underlying features contributing to this deterioration is lacking in pwMS. This study aimed at developing and validating such a model. METHODS: The gait of 24 healthy controls and 114 pwMS with mild, moderate, or severe disability was measured with inertial sensors on the shanks and lower trunk while walking for 6 minutes along a hospital corridor...
February 24, 2021: IEEE Transactions on Bio-medical Engineering
Ursula Muñoz, Cristina Sebal, Esther Escudero, Margaret Esiri, John Tzartos, Carolyn Sloan, Mari Cruz Sadaba
Antibodies and oxidative stress are hallmarks of multiple sclerosis (MS) lesions. We aimed to clarify the relation between them, their role in MS patients and to investigate their specificity, comparing MS with classical neurodegenerative diseases (ND). Brain samples from 14 MS cases, 6 with ND and 9 controls (without neurological diseases). Immunohistochemistry assays were used to detect oxidized lipids (EO6), IgG and IgM, oligodendrocytes (Olig2), axons (NF, neurofilament) and cellular (TUNEL) and axonal damage (APP, amyloid precursor protein)...
February 24, 2021: Cellular and Molecular Neurobiology
Brian C Healy
No abstract text is available yet for this article.
February 24, 2021: Multiple Sclerosis: Clinical and Laboratory Research
Carmen Tur
No abstract text is available yet for this article.
February 24, 2021: Multiple Sclerosis: Clinical and Laboratory Research
Massimiliano Copetti, Dawei Liu
No abstract text is available yet for this article.
February 24, 2021: Multiple Sclerosis: Clinical and Laboratory Research
Malene J Petersen, Sofie O Bergien, Dan Staerk
Multiple Sclerosis (MS) is a demyelinating disease affecting the central nervous system, with no curative medicine available. The use of herbal drugs and dietary supplements is increasing among people with MS (PwMS), raising a need for knowledge about potential interactions between conventional MS medicine and herbal drugs/dietary supplements. This systematic review provides information about the safety of simultaneous use of conventional MS-drugs and herbal drugs frequently used by PwMS. The study included 14 selected disease-modifying treatments and drugs frequently used for symptom-alleviation...
February 24, 2021: Phytotherapy Research: PTR
Natalie J Engmann, Danny Sheinson, Komal Bawa, Carmen D Ng, Gabriel Pardo
BACKGROUND: Ocrelizumab (OCR) is the only disease-modifying therapy (DMT) for both relapsing and primary progressive forms of multiple sclerosis (MS). OCR is given by intravenous (IV) infusion twice a year, which may improve adherence to the dosing schedule relative to other MS DMTs that require more frequent administration. Real-world evidence on the persistence and adherence of patients with MS to OCR compared with other DMTs is limited. OBJECTIVE: To examine the persistence and adherence to OCR compared with other DMTs for MS in the United States...
February 24, 2021: Journal of Managed Care & Specialty Pharmacy
Charidimos Tsagkas, Katrin Parmar, Simon Pezold, Christian Barro, Mallar M Chakravarty, Laura Gaetano, Yvonne Naegelin, Michael Amann, Athina Papadopoulou, Jens Wuerfel, Ludwig Kappos, Jens Kuhle, Till Sprenger, Cristina Granziera, Stefano Magon
There is evidence that multiple sclerosis (MS) pathology leads to distinct patterns of volume loss over time (VLOT) in different central nervous system (CNS) structures. We aimed to use such patterns to identify patient subgroups. MS patients of all classical disease phenotypes underwent annual clinical, blood, and MRI examinations over 6 years. Spinal, striatal, pallidal, thalamic, cortical, white matter, and T2-weighted lesion volumes as well as serum neurofilament light chain (sNfL) were quantified. CNS VLOT patterns were identified using principal component analysis and patients were classified using hierarchical cluster analysis...
February 24, 2021: Human Brain Mapping
Wojciech Danysz, Andrzej Dekundy, Astrid Scheschonka, Peter Riederer
The aim of the current review was to provide a new, in-depth insight into possible pharmacological targets of amantadine to pave the way to extending its therapeutic use to further indications beyond Parkinson's disease symptoms and viral infections. Considering amantadine's affinities in vitro and the expected concentration at targets at therapeutic doses in humans, the following primary targets seem to be most plausible: aromatic amino acids decarboxylase, glial-cell derived neurotrophic factor, sigma-1 receptors, phosphodiesterases, and nicotinic receptors...
February 23, 2021: Journal of Neural Transmission
Cecilie Jacobsen, Robert Zivadinov, Kjell-Morten Myhr, Turi O Dalaker, Ingvild Dalen, Ralph Hb Benedict, Niels Bergsland, Elisabeth Farbu
Objectives: To identify Magnetic Resonance Imaging (MRI), clinical and demographic biomarkers predictive of worsening information processing speed (IPS) as measured by Symbol Digit Modalities Test (SDMT). Methods: Demographic, clinical data and 1.5 T MRI scans were collected in 76 patients at time of inclusion, and after 5 and 10 years. Global and tissue-specific volumes were calculated at each time point. For the primary outcome of analysis, SDMT was used. Results: Worsening SDMT at 5-year follow-up was predicted by baseline age, Expanded Disability Status Scale (EDSS), SDMT, whole brain volume (WBV) and T2 lesion volume (LV), explaining 30...
January 2021: Multiple Sclerosis Journal—Experimental, Translational and Clinical
Michelle Drerup, Alicia Roth, Alexa Kane, Amy B Sullivan
The prevalence of sleep disorders in individuals with multiple sclerosis (MS) is 3-5 times higher compared to the general population. Insomnia Disorder, defined as difficulty falling asleep, maintaining sleep or waking up too early, can lead to significant fatigue, the most common and disabling symptom of MS. In addition, fatigue and insomnia in patients with MS also can overlap with and exacerbate other psychological and physical symptoms. Cognitive behavioral therapy for insomnia (CBT-I) has been shown as an effective treatment for chronic insomnia and burgeoning research has demonstrated the effectiveness of this treatment for insomnia in individuals with a variety of comorbid medical conditions including MS...
2021: Nature and Science of Sleep
Rebekka Rust, Claudia Chien, Michael Scheel, Alexander U Brandt, Jan Dörr, Jens Wuerfel, Katharina Klumbies, Hanna Zimmermann, Mario Lorenz, Klaus-Dieter Wernecke, Judith Bellmann-Strobl, Friedemann Paul
OBJECTIVE: To examine whether treatment with epigallocatechin gallate (EGCG) influences progression of brain atrophy, reduces clinical and further radiologic disease activity markers, and is safe in patients with progressive multiple sclerosis (PMS). METHODS: We enrolled 61 patients with primary or secondary PMS in a randomized double-blind, parallel-group, phase II trial on oral EGCG (up to 1,200 mg daily) or placebo for 36 months with an optional open-label EGCG treatment extension (OE) of 12-month duration...
May 2021: Neurology® Neuroimmunology & Neuroinflammation
Jordan Hoffmeister, Michael R Basso, Bradley Reynolds, Douglas Whiteside, Ryan Mulligan, Peter A Arnett, Dennis R Combs
Objective : Cognitive impairment affects as many as 65% of people with multiple sclerosis (PWMS), and memory impairment confers greater severity of disability and functional impairment. Depression is also common among PWMS, and lifetime prevalence rates are as high as 50%. Research has yet to clearly define the relationship between memory dysfunction and depression among PWMS, and may reflect incomplete assessment of depressive symptoms. The present study examined different aspects of depressive symptoms including anhedonia (i...
February 23, 2021: Journal of Clinical and Experimental Neuropsychology
Alexander Yermanos, Daniel Neumeier, Ioana Sandu, Mariana Borsa, Ann Cathrin Waindok, Doron Merkler, Annette Oxenius, Sai T Reddy
Neuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer's disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system. Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor and T cell receptor repertoires and accompanying gene expression profiles in young and old mouse brains...
February 24, 2021: Proceedings. Biological Sciences
Fanny Van Geel, Lars G Hvid, Pieter Van Noten, Bert O Eijnde, Ulrik Dalgas, Peter Feys
BACKGROUND: Both muscle fatigability and walking fatigability are prevalent in persons with MS (pwMS), but their associations remains unclear. The aim of this study was to examine the association of muscle strength and fatigability from both isometric and concentric protocols of three different muscle groups, and their association to walking capacity and walking fatigability. METHODS: Twenty-seven pwMS and 13 Healthy Controls (HC) were included in this exploratory study...
February 10, 2021: Multiple Sclerosis and related Disorders
Ting Wu, Yunxuan Lei, Shuxin Jin, Qing Zhao, Wenjing Cheng, Yebin Xi, Li Wang, Zhaojun Wang, Xiaoyin Niu, Guangjie Chen
Multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) are neuroinflammatory autoimmune diseases characterized by the axonal loss, demyelination, and neurodegeneration of the central nervous system. Overactivation of CD4+ T cells, especially the migration of the Th1 and Th17 subsets into the central nervous system (CNS), leads to the secretion of inflammatory mediators and destruction of the contact between neurons and activated macrophages, which can then result in a series of neurocognitive and motor deficits...
February 20, 2021: Molecular Immunology
Robert A Bermel, Emmanuelle Waubant, Gabriel Pardo, Ann Bass, Pavle Repovic, Scott Newsome, John W Lindsey, Deidre Kile, Ashish Pradhan, Bruno Musch, Aram Zabeti
The CHORDS trial evaluated ocrelizumab (OCR) in patients with relapsing-remitting multiple sclerosis who had a suboptimal response to previous disease-modifying treatment. The objective of the present study was to assess the safety of shorter OCR infusions in a substudy of CHORDS. After completing four doses of OCR per initial US prescribing recommendations in the main study, participants in the substudy (N = 129) received a fifth dose over a 2-h duration (vs. 3.5 h). Infusion-related reactions occurred in 12...
February 23, 2021: Annals of Clinical and Translational Neurology
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