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ALS Therapy

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https://www.readbyqxmd.com/read/28533210/specific-biomarkers-for-c9orf72-ftd-als-could-expedite-the-journey-towards-effective-therapies
#1
Rubika Balendra, Thomas G Moens, Adrian M Isaacs
No abstract text is available yet for this article.
May 22, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28523551/epigenetic-mechanisms-of-gene-regulation-in-amyotrophic-lateral-sclerosis
#2
Alba Jimenez-Pacheco, Jaime M Franco, Soledad Lopez, Juan Miguel Gomez-Zumaquero, Maria Magdalena Leal-Lasarte, Diana E Caballero-Hernandez, Marta Cejudo-Guillén, David Pozo
Despite being clinically described 150 years ago, the mechanisms underlying amyotrophic lateral sclerosis (ALS) pathogenesis have not yet been fully understood. Studies in both animal models of ALS and human patients reveal a plethora of alterations such as increased glutamate-mediated excitotoxicity, redox stress, increased apoptosis, defective axonal transport, protein-misfolding events, mitochondrial impairment and sustained unregulated immune responses. Regardless of being sporadic or familiar ALS, the final outcome at the cellular level is the death of upper and lower motor neurons, and once diagnosed, ALS is typically lethal within the next 5 years...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28500219/mechanisms-of-enhanced-phrenic-long-term-facilitation-in-sod1-g93a-rats
#3
Nicole L Nichols, Irawan Satriotomo, Latoya L Allen, Ashley M Grebe, Gordon S Mitchell
Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease, causing muscle paralysis and death from respiratory failure. Effective means to preserve/restore ventilation are necessary to increase the quality and duration of life in ALS patients. At disease end-stage in a rat ALS model (SOD1(G93A)), acute intermittent hypoxia (AIH) restores phrenic nerve activity to normal levels via enhanced phrenic long-term facilitation (pLTF). Mechanisms enhancing pLTF in end-stage SOD1(G93A) rats are not known...
May 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28490573/dok7-gene-therapy-enhances-motor-activity-and-life-span-in-als-model-mice
#4
Sadanori Miyoshi, Tohru Tezuka, Sumimasa Arimura, Taro Tomono, Takashi Okada, Yuji Yamanashi
Amyotrophic lateral sclerosis (ALS) is a progressive, multifactorial motor neurodegenerative disease with severe muscle atrophy. The glutamate release inhibitor riluzole is the only medication approved by the FDA, and prolongs patient life span by a few months, testifying to a strong need for new treatment strategies. In ALS, motor neuron degeneration first becomes evident at the motor nerve terminals in neuromuscular junctions (NMJs), the cholinergic synapse between motor neuron and skeletal muscle; degeneration then progresses proximally, implicating the NMJ as a therapeutic target...
May 10, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28485867/die-chronische-ven%C3%A3-se-insuffizienz-eine-zusammenfassung-der-pathophysiologie-diagnostik-und-therapie
#5
Bettina Santler, Tobias Goerge
Die chronische Venenerkrankung ist eine weit verbreitete Krankheit, die in späteren Stadien mit einer Vielzahl an Symptomen, aber auch Komplikationen wie dem Ulcus cruris, einhergeht. Dies wiederum hat weitreichende Auswirkungen auf die Lebensqualität der Patienten wie auch auf das Gesundheitssystem. Für die Diagnostik der chronischen Venenerkrankungen steht eine Auswahl an Verfahren zur Verfügung, wobei sich die farbkodierte Duplexsonographie als Goldstandard etabliert hat. Im Bereich der Therapie kam es in den letzten Jahrzehnten zu großen Fortschritten, sodass heute auch Alternativen zum klassischen Stripping durch die endoluminalen Verfahren zur Verfügung stehen...
May 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28479121/ethical-considerations-and-palliative-care-in-patients-with-amyotrophic-lateral-sclerosis-a-review
#6
REVIEW
V Danel-Brunaud, L Touzet, L Chevalier, C Moreau, D Devos, S Vandolaeghe, L Defebvre
Amyotrophic lateral sclerosis (ALS) is not a curable disease, but it is treatable. By definition, much of the care provided to ALS patients is palliative, even though active life-sustaining strategies are available to prolong survival. Healthcare professionals must develop communication skills that help patients cope with the inexorable progression of the disease and the inevitability of death. Symptomatic treatments as well as respiratory insufficiency and nutritional life-sustaining therapies must be regularly evaluated as the disease progresses, without losing sight of the burden placed on the patient's non-professional caregivers...
May 4, 2017: Revue Neurologique
https://www.readbyqxmd.com/read/28469596/molecular-taxonomy-of-sporadic-amyotrophic-lateral-sclerosis-using-disease-associated-genes
#7
Giovanna Morello, Antonio Gianmaria Spampinato, Sebastiano Cavallaro
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of upper and lower motor neurons. Despite intensive research, the origin and progression of ALS remain largely unknown, suggesting that the traditional clinical diagnosis and treatment strategies might not be adequate to completely capture the molecular complexity underlying the disease. In our previous work, comprehensive genomic profiling of 41 motor cortex samples enabled to discriminate control from sporadic ALS patients and segregated these latter into two distinct subgroups, each associated with different deregulated genes and pathways...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28448871/immunomodulatory-effects-of-stem-cells-therapeutic-option-for-neurodegenerative-disorders
#8
REVIEW
Martin Caprnda, Peter Kubatka, Katarina Gazdikova, Iveta Gasparova, Vanda Valentova, Nadezda Stollarova, Giampiero La Rocca, Nazarii Kobyliak, Jozef Dragasek, Ioana Mozos, Robert Prosecky, Dario Siniscalco, Dietrich Büsselberg, Luis Rodrigo, Peter Kruzliak
Stem cells have the capability of self-renewal and can differentiate into different cell types that might be used in regenerative medicine. Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently lack effective treatments. Although stem cell therapy is still on the way from bench to bedside, we consider that it might provide new hope for patients suffering with neurodegenerative diseases. In this article, we will give an overview of recent studies on the potential therapeutic use of mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and perinatal stem cells to neurodegenerative disorders and we will describe their immunomodulatory mechanisms of action in specific therapeutic modalities...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28443372/cord-blood-as-a-potential-therapeutic-for-amyotrophic-lateral-sclerosis
#9
Svitlana Garbuzova-Davis, Jared Ehrhart, Paul R Sanberg
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord. Treatment options are limited due to the complexity of underlying disease factors. Cell therapy, using human umbilical cord blood (hUCB) cells may be a promising new treatment for ALS, mainly by providing a protective microenvironment for motor neuron survival. Areas covered: Composition, in vitro and in vivo differentiation of hUCB cells, and the advantages of cord blood as a source of transplant cells are discussed...
May 8, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28437540/characterization-of-gene-expression-phenotype-in-amyotrophic-lateral-sclerosis-monocytes
#10
Weihua Zhao, David R Beers, Kristopher G Hooten, Douglas H Sieglaff, Aijun Zhang, Shanker Kalyana-Sundaram, Christopher M Traini, Wendy S Halsey, Ashley M Hughes, Ganesh M Sathe, George P Livi, Guo-Huang Fan, Stanley H Appel
Importance: Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by selective loss of upper and lower motor neurons. Patients with ALS have persistent peripheral and central inflammatory responses including abnormally functioning T cells and activated microglia. However, much less is known about the inflammatory gene profile of circulating innate immune monocytes in these patients. Objective: To characterize the transcriptomics of peripheral monocytes in patients with ALS...
April 24, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28422386/corticosteroid-might-reduce-serum-levels-of-pro-inflammatory-cytokines-in-fulminant-hepatitis-a-case-series
#11
Keiichi Fujiwara, Seiji Hida, Shin Yasui, Osamu Yokosuka, Shigeto Oda
AIM: There are no beneficial therapies except for emergency liver transplantation for acute liver failure (ALF). However, in Japan, which has a serious problem in the shortage of donor livers, therapies other than transplantation must be further investigated for patients with ALF. Pro-inflammatory cytokines promoting tissue destruction are predominant at an early phase of ALF. Corticosteroid (CS) influences monocyte/macrophage differentiation, by suppressing pro-inflammatory genes, indicating CS treatment might be beneficial during the early phase of ALF...
April 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28416596/microrna-profiling-reveals-marker-of-motor-neuron-disease-in-als-models
#12
Mariah L Hoye, Erica D Koval, Amy J Wegener, Theodore S Hyman, Chengran Yang, David R O'Brien, Rebecca L Miller, Tracy Cole, Kathleen M Schoch, Tao Shen, Tomonori Kunikata, Jean-Philippe Richard, David H Gutmann, Nicholas J Maragakis, Holly B Kordasiewicz, Joseph D Dougherty, Timothy M Miller
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type in order to elucidate underlying disease mechanisms and identify novel targets that inform on MN health during ALS disease timecourse. microRNAs (miRNAs) are short, non-coding RNAs that can shape the expression profile of a cell and, consequently, often exhibit cell type enriched expression...
April 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28409282/motor-neuron-vulnerability-and-resistance-in-amyotrophic-lateral-sclerosis
#13
REVIEW
Jik Nijssen, Laura H Comley, Eva Hedlund
In the fatal disease-amyotrophic lateral sclerosis (ALS)-upper (corticospinal) motor neurons (MNs) and lower somatic MNs, which innervate voluntary muscles, degenerate. Importantly, certain lower MN subgroups are relatively resistant to degeneration, even though pathogenic proteins are typically ubiquitously expressed. Ocular MNs (OMNs), including the oculomotor, trochlear and abducens nuclei (CNIII, IV and VI), which regulate eye movement, persist throughout the disease. Consequently, eye-tracking devices are used to enable paralysed ALS patients (who can no longer speak) to communicate...
June 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28406335/clinical-efficacy-of-edaravone-for-the-treatment-of-amyotrophic-lateral-sclerosis
#14
Hideyuki Sawada
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease. Although the pathogenesis remains unresolved, oxidative stress is known to play a pivotal role. Edaravone works in the central nervous system as a potent scavenger of oxygen radicals. In ALS mouse models, edaravone suppresses motor functional decline and nitration of tyrosine residues in the cerebrospinal fluid. Areas covered: Three clinical trials, one phase II open-label trial, and two phase III placebo-control randomized trials were reviewed...
May 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28405022/therapeutic-reduction-of-ataxin-2-extends-lifespan-and-reduces-pathology-in-tdp-43-mice
#15
Lindsay A Becker, Brenda Huang, Gregor Bieri, Rosanna Ma, David A Knowles, Paymaan Jafar-Nejad, James Messing, Hong Joo Kim, Armand Soriano, Georg Auburger, Stefan M Pulst, J Paul Taylor, Frank Rigo, Aaron D Gitler
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease that is characterized by motor neuron loss and that leads to paralysis and death 2-5 years after disease onset. Nearly all patients with ALS have aggregates of the RNA-binding protein TDP-43 in their brains and spinal cords, and rare mutations in the gene encoding TDP-43 can cause ALS. There are no effective TDP-43-directed therapies for ALS or related TDP-43 proteinopathies, such as frontotemporal dementia. Antisense oligonucleotides (ASOs) and RNA-interference approaches are emerging as attractive therapeutic strategies in neurological diseases...
April 20, 2017: Nature
https://www.readbyqxmd.com/read/28397314/supporting-clinical-leadership-through-action-the-nurse-consultant-role
#16
Elizabeth Rosser, Rachael Grey, Deborah Neal, Julie Reeve, Caroline Smith, Janine Valentine
The aim is to evaluate the effectiveness of an action learning set (ALS) to enhance clinical leadership and extend their scope and confidence more strategically. BACKGROUND: As the most senior clinical role in most healthcare systems, the consultant nurse role is a solitary one. They are required to develop personal resilience, commitment and a belief in their ability to lead, with new consultants needing a strong support network to succeed. DESIGN: Following a two year ALS, four nurse consultants, one therapy consultant, and a university educationalist engaged in a co-operative inquiry approach using four cycles of discussion, reflection, analysis and action over an 18 month period from March 2015 - July 2016, to learn how to change and enhance their working practices...
April 10, 2017: Journal of Clinical Nursing
https://www.readbyqxmd.com/read/28387447/withdrawn-interventions-for-fatigue-and-weight-loss-in-adults-with-advanced-progressive-illness
#17
REVIEW
Cathy Payne, Philip J Wiffen, Suzanne Martin
BACKGROUND: Fatigue and unintentional weight loss are two of the commonest symptoms experienced by people with advanced progressive illness. Appropriate interventions may bring considerable improvements in function and quality of life to seriously ill people and their families, reducing physical, psychological and spiritual distress. OBJECTIVES: To conduct an overview of the evidence available on the efficacy of interventions used in the management of fatigue and/or unintentional weight loss in adults with advanced progressive illness by reviewing the evidence contained within Cochrane reviews...
April 7, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28377696/als-pathogenesis-and-therapeutic-approaches-the-role-of-mesenchymal-stem-cells-and-extracellular-vesicles
#18
REVIEW
Roberta Bonafede, Raffaella Mariotti
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle paralysis determined by the degeneration of motoneurons in the motor cortex brainstem and spinal cord. The ALS pathogenetic mechanisms are still unclear, despite the wealth of studies demonstrating the involvement of several altered signaling pathways, such as mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress and neuroinflammation. To date, the proposed therapeutic strategies are targeted to one or a few of these alterations, resulting in only a minimal effect on disease course and survival of ALS patients...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28365708/resistenzentwicklung-und-pr%C3%A3-diktive-marker-beim-metastasierten-prostatakarzinom
#19
Christof Bernemann, Martin Bögemann, Julie Steinestel, Andreas Jan Schrader
Anders als bei vielen anderen Krebserkrankungen gab es beim Prostatakarzinom lange Zeit keinen Ansatz für eine individualisierte Therapie. Seit der Zulassung von mehreren modernen Wirkstoffen für die Therapie des fortgeschrittenen Stadiums ändert sich dies allmählich. Zunächst galt die Androgenrezeptor-Splice-Variante AR-V7 als vielversprechender Biomarker für die Therapiesteuerung, woran sich zunehmend Zweifel mehren. Inzwischen gibt es jedoch eine Reihe von weiteren neuen, noch nicht zugelassenen und nicht (nur) auf den Androgenrezeptor fokussierenden Therapieansätzen, die auch beim fortgeschrittenen Prostatakarzinom eine personalisierte Medizin wahrscheinlicher machen...
2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28364247/intracerebroventricular-delivery-in-mice-for-motor-neuron-diseases
#20
M Nizzardo, M Rizzuti
The use of antisense oligonucleotides to target specific mRNA sequences represents a promising therapeutic strategy for neurological disorders. Recent advances in antisense technology enclose the development of phosphorodiamidate morpholino oligomers (MO), which is one of the best candidates for molecular therapies due to MO's excellent pharmacological profile.Nevertheless, the route of administration of antisense compounds represents a critical issue in the neurological field. Particularly, as regards motor neuron diseases, intracerebroventricular (ICV) injection is undoubtedly the most efficient procedure to directly deliver therapeutic molecules in the central nervous system (CNS)...
2017: Methods in Molecular Biology
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