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ALS Therapy

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https://www.readbyqxmd.com/read/29666294/laryngeal-responses-to-mechanically-assisted-cough-in-progressing-amyotrophic-lateral-sclerosis
#1
Tiina M Andersen, Astrid Sandnes, Ove Fondenes, Roy M Nilsen, Ole-Bjørn Tysnes, John-Helge Heimdal, Hege H Clemm, Thomas Halvorsen, Maria Vollsœter, Ola D Røksund
BACKGROUND: Respiratory complications represent the major cause of death in amyotrophic lateral sclerosis (ALS). Noninvasive respiratory support is the mainstay therapy, but treatment becomes challenging as the disease progresses, possibly due to a malfunctioning larynx, which is the entrance to the airways. We studied laryngeal response patterns to mechanically assisted cough (mechanical insufflation-exsufflation) as ALS progresses. METHODS: This prospective longitudinal study of 13 consecutively included subjects with ALS were followed up during 2011-2016 with repeated tests of lung function, neurological status, and laryngeal responses to mechanical insufflation-exsufflation using video-recorded flexible transnasal fiberoptic laryngoscopy...
April 17, 2018: Respiratory Care
https://www.readbyqxmd.com/read/29656576/repurposing-carbamazepine-for-the-treatment-of-amyotrophic-lateral-sclerosis-in-sod1-g93a-mouse-model
#2
Jing-Jing Zhang, Qin-Ming Zhou, Sheng Chen, Wei-Dong Le
AIMS: To investigate the effect and mechanisms of carbamazepine (CBZ) on the onset and progression of amyotrophic lateral sclerosis (ALS) in SOD1-G93A mouse model. METHODS: Starting from 64 days of age, SOD1-G93A mice were orally administered with CBZ at 200 mg/kg once daily until death. The disease onset and life span of SOD1-G93A mice were recorded. Motor neurons (MNs) in anterior horn of spinal cord were quantified by Nissl staining and SMI-32 immunostaining...
April 14, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29625589/intramuscular-transplantation-of-bone-marrow-cells-prolongs-the-lifespan-of-sod1-g93a-mice-and-modulates-expression-of-prognosis-biomarkers-of-the-disease
#3
Amaya Rando, Diego Pastor, Mari Carmen Viso-León, Anna Martínez, Raquel Manzano, Xavier Navarro, Rosario Osta, Salvador Martínez
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis and death. There is no effective treatment for ALS and stem cell therapy has arisen as a potential therapeutic approach. METHODS: SOD1 mutant mice were used to study the potential neurotrophic effect of bone marrow cells grafted into quadriceps femoris muscle. RESULTS: Bone marrow intramuscular transplants resulted in increased longevity with improved motor function and decreased motoneuron degeneration in the spinal cord...
April 6, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29618798/differential-expression-of-micrornas-and-other-small-rnas-in-muscle-tissue-of-patients-with-als-and-healthy-age-matched-controls
#4
Anja Kovanda, Lea Leonardis, Janez Zidar, Blaž Koritnik, Leja Dolenc-Groselj, Stanislava Ristic Kovacic, Tomaž Curk, Boris Rogelj
Amyotrophic lateral sclerosis is a late-onset disorder primarily affecting motor neurons and leading to progressive and lethal skeletal muscle atrophy. Small RNAs, including microRNAs (miRNAs), can serve as important regulators of gene expression and can act both globally and in a tissue-/cell-type-specific manner. In muscle, miRNAs called myomiRs govern important processes and are deregulated in various disorders. Several myomiRs have shown promise for therapeutic use in cellular and animal models of ALS; however, the exact miRNA species differentially expressed in muscle tissue of ALS patients remain unknown...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29615862/serotonergic-dysfunction-in-amyotrophic-lateral-sclerosis-and-parkinson-s-disease-similar-mechanisms-dissimilar-outcomes
#5
Yannick Vermeiren, Jana Janssens, Debby Van Dam, Peter P De Deyn
Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) share similar pathophysiological mechanisms. From a neurochemical point of view, the serotonin (5-hydroxytryptamine; 5-HT) dysfunction in both movement disorders-related to probable lesioning of the raphe nuclei-is profound, and, therefore, may be partially responsible for motor as well as non-motor disturbances. More specifically, in ALS, it has been hypothesized that serotonergic denervation leads to loss of its inhibitory control on glutamate release, resulting into glutamate-induced neurotoxicity in lower and/or upper motor neurons, combined with a detrimental decrease of its facilitatory effects on glutamatergic motor neuron excitation...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29605155/als-genes-in-the-genomic-era-and-their-implications-for-ftd
#6
REVIEW
Hung Phuoc Nguyen, Christine Van Broeckhoven, Julie van der Zee
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient-control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential relevance to frontotemporal dementia genetic etiology...
March 28, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29593492/enteroviral-infection-the-forgotten-link-to-amyotrophic-lateral-sclerosis
#7
REVIEW
Yuan Chao Xue, Ralph Feuer, Neil Cashman, Honglin Luo
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that primarily attacks motor neurons in the brain and spinal cord, leading to progressive paralysis and ultimately death. Currently there is no effective therapy. The majority of ALS cases are sporadic, with no known family history; unfortunately the etiology remains largely unknown. Contribution of Enteroviruses (EVs), a family of positive-stranded RNA viruses including poliovirus, coxsackievirus, echovirus, enterovirus-A71 and enterovirus-D68, to the development of ALS has been suspected as they can target motor neurons, and patients with prior poliomyelitis show a higher risk of motor neuron disease...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29592535/commentary-on-some-recent-theses-relevant-to-combating-aging-april-2018
#8
Benjamin Zealley, Aubrey D N J de Grey
Theses reviewed in this issue include "An Intranasal GDNF Gene Therapy Approach for Treating Parkinson's Disease", "Controlling Depth of Cellular Quiescence By an Rb-E2F Network Switch", "Immunoregulation of the Central Response to Peripheral Nerve Injury: Motoneuron Survival and Relevance to ALS", and "Single-Cell Whole-Genome Sequencing Reveals Widespread Somatic Copy Number Variations in the Developing Cerebral Cortex".
March 28, 2018: Rejuvenation Research
https://www.readbyqxmd.com/read/29590675/influence-of-scan-time-point-and-volume-of-intravenous-contrast-administration-on-blood-pool-and-liver-suvmax-and-suvmean-in-18f-fdg-pet-ct
#9
Matthias Schoen, Timm Braun, Panagiota Manava, Sigrid Ludwigs, Michael Lell
AIM: To investigate the influence of scan time point and volume of intravenous contrast material in 18F-FDG PET/CT on maximum and mean standardized uptake values (SUVmax /mean ) in bloodpool and liver. METHODS: In 120 patients scheduled for routine whole-body 18F-FDG PET/CT the maximum and mean standardized uptake values (SUVmax /SUVmean ) in the liver and blood pool were measured after varying scan time-point (delay 0 s-140 s post injectionem) and volume of contrast material (CM; 0 ml, 80 ml, 100 ml of 300 mg/ml of Iodine)...
April 2018: Nuklearmedizin. Nuclear Medicine
https://www.readbyqxmd.com/read/29577886/mouse-models-of-als-past-present-and-future
#10
Cathleen Lutz
Genome sequencing of both sporadic and familial patients of Amyotrophic Lateral Sclerosis (ALS) has led to the identification of new genes that are both contributing and causative in the disease. This gene discovery has come at an unprecedented rate, and much of it in recent years. Knowledge of these genetic mutations provides us with opportunities to uncover new and related mechanisms, increasing our understanding of the disease and bringing us closer to defined therapies for patients. Mouse models have played an important role in our current understanding of the pathophysiology of ALS and have served as important preclinical models in testing new therapeutics...
March 22, 2018: Brain Research
https://www.readbyqxmd.com/read/29576321/an-intracellular-allosteric-modulator-binding-pocket-in-sk2-ion-channels-is-shared-by-multiple-chemotypes
#11
Lily T-Y Cho, Aristos J Alexandrou, Rubben Torella, John Knafels, Jake Hobbs, Toni Taylor, Alex Loucif, Agnieszka Konopacka, Sigourney Bell, Edward B Stevens, Jay Pandit, Reto Horst, Jane M Withka, David C Pryde, Shenping Liu, Gareth T Young
Small conductance potassium (SK) ion channels define neuronal firing rates by conducting the after-hyperpolarization current. They are key targets in developing therapies where neuronal firing rates are dysfunctional, such as in epilepsy, Parkinson's, and amyotrophic lateral sclerosis (ALS). Here, we characterize a binding pocket situated at the intracellular interface of SK2 and calmodulin, which we show to be shared by multiple small-molecule chemotypes. Crystallization of this complex revealed that riluzole (approved for ALS) and an analog of the anti-ataxic agent (4-chloro-phenyl)-[2-(3,5-dimethyl-pyrazol-1-yl)-pyrimidin-4-yl]-amine (CyPPA) bind to and allosterically modulate via this site...
March 19, 2018: Structure
https://www.readbyqxmd.com/read/29562705/crispr-cas9-technology-as-an-emerging-tool-for-targeting-amyotrophic-lateral-sclerosis-als
#12
REVIEW
Ewa Kruminis-Kaszkiel, Judyta Juranek, Wojciech Maksymowicz, Joanna Wojtkiewicz
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) is a genome editing tool that has recently caught enormous attention due to its novelty, feasibility, and affordability. This system naturally functions as a defense mechanism in bacteria and has been repurposed as an RNA-guided DNA editing tool. Unlike zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), CRISPR/Cas9 takes advantage of an RNA-guided DNA endonuclease enzyme, Cas9, which is able to generate double-strand breaks (DSBs) at specific genomic locations...
March 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29545836/gemals-a-promising-therapy-for-amyotrophic-lateral-sclerosis
#13
Michel Geffard, Arturo Mangas, Denis Bedat, Rafael Coveñas
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that currently has no cure. At present, the only approved treatment for ALS is Riluzole, a glutamate release blocker that improves life expectancy by 3-6 months. ALS-Endotherapia (GEMALS) is a novel therapeutic approach to treat ALS and the aim of the present study was to investigate the potential beneficial effects of this novel treatment. A total of 31 patients with ALS were assessed in the current study. Deceleration of the disease was observed in 83...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29537158/umgang-mit-antithrombotika-bei-operationen-an-der-haut-vor-und-nach-publikation-der-entsprechenden-s3-leitlinie
#14
Matthew Gaskins, Martin Dittmann, Lisa Eisert, Ricardo Niklas Werner, Corinna Dressler, Christoph Löser, Alexander Nast
HINTERGRUND: Laut einer Befragung im Jahre 2012 war der Umgang mit Antithrombotika bei dermatochirurgischen Eingriffen in Deutschland sehr heterogen. 2014 wurde erstmals eine evidenzbasierte Leitlinie zu diesem Thema veröffentlicht. METHODIK: Es wurde eine anonyme Befragung derselben Stichprobe zum Umgang mit Antithrombotika sowie zu Kenntnissen der Leitlinie durchgeführt. Die Ergebnisse wurden als relative Häufigkeiten berichtet und denen aus 2012 gegenübergestellt...
March 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/29529995/dissecting-the-pathobiology-of-altered-mri-signal-in-amyotrophic-lateral-sclerosis-a-post-mortem-whole-brain-sampling-strategy-for-the-integration-of-ultra-high-field-mri-and-quantitative-neuropathology
#15
Menuka Pallebage-Gamarallage, Sean Foxley, Ricarda A L Menke, Istvan N Huszar, Mark Jenkinson, Benjamin C Tendler, Chaoyue Wang, Saad Jbabdi, Martin R Turner, Karla L Miller, Olaf Ansorge
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a clinically and histopathologically heterogeneous neurodegenerative disorder, in which therapy is hindered by the rapid progression of disease and lack of biomarkers. Magnetic resonance imaging (MRI) has demonstrated its potential for detecting the pathological signature and tracking disease progression in ALS. However, the microstructural and molecular pathological substrate is poorly understood and generally defined histologically...
March 13, 2018: BMC Neuroscience
https://www.readbyqxmd.com/read/29523587/characterisation-of-mesenchymal-stem-cells-from-patients-with-amyotrophic-lateral-sclerosis
#16
Nicole Matejckova, Alena Zajicova, Barbora Hermankova, Jan Kossl, Pavla Bohacova, Vladimir Holan, Eliska Javorkova
AIMS: Mesenchymal stem cells (MSCs) have recently been tested in clinical trials to treat severe diseases, including amyotrophic lateral sclerosis (ALS). Since autologous MSCs are frequently used for therapy, we aimed to evaluate the possible influence of the disease on characteristics and function of these cells. METHODS: MSCs were isolated from the bone marrow of patients with ALS and compared with MSCs from healthy controls (HC). The cells were tested for phenotype, growth properties, differentiation ability, metabolic activity, secretory potential, expression of genes for immunomodulatory molecules and for the ability to regulate proliferation of mitogen-stimulated peripheral blood leucocytes...
March 9, 2018: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29510461/mexiletine-for-muscle-cramps-in-als-a-randomized-double-blind-crossover-trial
#17
Björn Oskarsson, Dan Moore, Tahseen Mozaffar, John Ravits, Martina Wiedau-Pazos, Nicholas Parziale, Nanette C Joyce, Ross Mandeville, Namita Goyal, Merit E Cudkowicz, Michael Weiss, Robert G Miller, Craig M McDonald
INTRODUCTION: More than 90% of amyotrophic lateral sclerosis (ALS) patients have muscle cramps, and evidence-based treatments have not been available. METHODS: A multicenter double-blind placebo-controlled crossover trial of mexiletine 150 mg twice daily was conducted of ALS patients requesting treatment of symptomatic muscle cramps. RESULTS: Muscle cramp frequency was reduced in 18 of 20 patients; 13 reductions were attributed to treatment (P<...
March 6, 2018: Muscle & Nerve
https://www.readbyqxmd.com/read/29504729/possible-etiology-and-treatment-of-amyotrophic-lateral-sclerosis
#18
Václav Holecek, Richard Rokyta
Amyotrophic Lateral Sclerosis (ALS) is one of the most dangerous and least understood diseases with a pathophysiology that is still largely unknown. In this article we try to provide a pathophysiological explanation of the etiological, pathogenetic, and clinical aspects of ALS. After a description of the rather complicated classification of the disease, we continue with an evaluation of its clinical presentation. The bibliography reveals several suspect etiological factors including atherosclerosis, inflammation, tumors, cataracts, diabetes mellitus type 2, aging, and degeneration of the nervous system...
February 2018: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/29495962/rns60-exerts-therapeutic-effects-in-the-sod1-als-mouse-model-through-protective-glia-and-peripheral-nerve-rescue
#19
Antonio Vallarola, Francesca Sironi, Massimo Tortarolo, Noemi Gatto, Roberta De Gioia, Laura Pasetto, Massimiliano De Paola, Alessandro Mariani, Supurna Ghosh, Richard Watson, Andreas Kalmes, Valentina Bonetto, Caterina Bendotti
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects the motor neuromuscular system leading to complete paralysis and premature death. The multifactorial nature of ALS that involves both cell-autonomous and non-cell-autonomous processes contributes to the lack of effective therapies, usually targeted to a single pathogenic mechanism. RNS60, an experimental drug containing oxygenated nanobubbles generated by modified Taylor-Couette-Poiseuille flow with elevated oxygen pressure, has shown anti-inflammatory and neuroprotective properties in different experimental paradigms...
March 1, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29472887/a-possible-role-for-platelet-activating-factor-receptor-in-amyotrophic-lateral-sclerosis-treatment
#20
Marcelo R S Briones, Amanda M Snyder, Renata C Ferreira, Elizabeth B Neely, James R Connor, James R Broach
Amyotrophic lateral sclerosis (ALS) is the third most prevalent neurodegenerative disease affecting upper and lower motor neurons. An important pathway that may lead to motor neuron degeneration is neuroinflammation. Cerebrospinal Fluids of ALS patients have increased levels of the inflammatory cytokine IL-18. Because IL-18 is produced by dendritic cells stimulated by the platelet-activating factor (PAF), a major neuroinflammatory mediator, it is expected that PAF is involved in ALS. Here we show pilot experimental data on amplification of PAF receptor (PAFR) mRNA by RT-PCR...
2018: Frontiers in Neurology
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