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ALS Therapy

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https://www.readbyqxmd.com/read/28087719/genetics-insight-into-the-amyotrophic-lateral-sclerosis-frontotemporal-dementia-spectrum
#1
REVIEW
Ai-Ling Ji, Xia Zhang, Wei-Wei Chen, Wen-Juan Huang
Recent genetic discoveries have dramatically changed our understanding of two major neurodegenerative conditions. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are common, devastating diseases of the brain. For decades, ALS and FTD were classified as movement and cognitive disorders, respectively, due to their distinct clinical phenotypes. The recent identification of chromosome 9 open reading frame 72 (C9orf72) as the major gene causative of familial forms of ALS and FTD uncovered a new reality of a continuous FTD/ALS spectrum...
January 13, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28072907/symptomatic-treatments-for-amyotrophic-lateral-sclerosis-motor-neuron-disease
#2
REVIEW
Louisa Ng, Fary Khan, Carolyn A Young, Mary Galea
BACKGROUND: Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited. OBJECTIVES: To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND. METHODS: We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND...
January 10, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28038988/serial-in-vivo-imaging-of-transplanted-allogeneic-neural-stem-cell-survival-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#3
Amit K Srivastava, Sarah K Gross, Akshata A Almad, Camille A Bulte, Nicholas J Maragakis, Jeff W M Bulte
Neural stem cells (NSCs) are being investigated as a possible treatment for amyotrophic lateral sclerosis (ALS) through intraspinal transplantation, but no longitudinal imaging studies exist that describe the survival of engrafted cells over time. Allogeneic firefly luciferase-expressing murine NSCs (Luc(+)-NSCs) were transplanted bilaterally (100,000 cells/2μl) into the cervical spinal cord (C5) parenchyma of pre-symptomatic (63day-old) SOD1(G93A) ALS mice (n=14) and wild-type age-matched littermates (n=14)...
December 28, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28025800/intrathecal-delivery-of-ssaav9-dao-extends-survival-in-sod1-g93a-als-mice
#4
Wan Wang, Weisong Duan, Ying Wang, Di Wen, Yakun Liu, Zhongyao Li, Haojie Hu, Hongying Cui, Can Cui, Huiqian Lin, Chunyan Li
Amyotrophic lateral sclerosis (ALS) is an adult-onset, irreversible neurodegenerative disease that leads to progressive paralysis and inevitable death 3-5 years after diagnosis. The mechanisms underlying this process remain unknown, but new evidence indicates that accumulating levels of D-serine result from the downregulation of D-amino acid oxidase (DAO) and that this is a novel mechanism that leads to motoneuronal death in ALS via N-methyl-D-aspartate receptor-mediated cell toxicity. Here, we explored a new therapeutic approach to ALS by overexpressing DAO in the lumbar region of the mouse spinal cord using a single stranded adeno-associated virus serotype 9 (ssAAV9) vector...
December 26, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/28011744/targeting-extracellular-cyclophilin-a-reduces-neuroinflammation-and-extends-survival-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#5
Laura Pasetto, Silvia Pozzi, Mariachiara Castelnovo, Manuela Basso, Alvaro G Estevez, Stefano Fumagalli, Maria Grazia De Simoni, Valeria Castellaneta, Paolo Bigini, Elena Restelli, Roberto Chiesa, Francesca Trojsi, Maria Rosaria Monsurrò, Leonardo Callea, Miroslav Malešević, Gunter Fischer, Mattia Freschi, Massimo Tortarolo, Caterina Bendotti, Valentina Bonetto
: Neuroinflammation is a major hallmark of amyotrophic lateral sclerosis (ALS), which is currently untreatable. Several anti-inflammatory compounds have been evaluated in patients and animal models of ALS, but have been proved disappointing, in part because effective targets have not yet been identified. Cyclophilin A (PPIA) as a foldase is beneficial intracellularly, but extracellularly has detrimental functions. We found that extracellular PPIA is a mediator of neuroinflammation in ALS...
December 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28009271/bidirectional-transcriptional-inhibition-as-therapy-for-als-ftd-caused-by-repeat-expansion-in-c9orf72
#6
Jie Jiang, Don W Cleveland
Hexanucleotide repeat expansion in the bi-directionally transcribed C9orf72 gene is the most frequent cause of familial ALS and frontotemporal dementia (FTD). Kramer et al. (2016) report in Science that targeted reduction in the transcription elongation factor SUPT4H1/SUPT5H reduces both sense and antisense repeat-containing RNAs and their associated neurodegeneration.
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/27999880/-pathomechanisms-and-clinical-aspects-of-frontotemporal-lobar-degeneration
#7
REVIEW
K Bürger, T Arzberger, J Stephan, J Levin, D Edbauer
BACKGROUND: Frontotemporal lobar degeneration (FTLD) includes a spectrum of heterogeneous clinical and neuropathological diseases. In a strict sense this includes the behavioral variant of frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA) and both variants can be associated with amyotrophic lateral sclerosis (FTD-ALS). In a broader sense FTLD also includes progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). In recent years the strong genetic component of FTLD has become increasingly clear...
December 20, 2016: Der Nervenarzt
https://www.readbyqxmd.com/read/27995572/intramuscular-delivery-of-scaav9-higf1-prolongs-survival-in-the-hsod1-g93a-als-mouse-model-via-upregulation-of-d-amino-acid-oxidase
#8
HuiQian Lin, HaoJie Hu, WeiSong Duan, YaLing Liu, GuoJun Tan, ZhongYao Li, YaKun Liu, BinBin Deng, XueQin Song, Wan Wang, Di Wen, Ying Wang, ChunYan Li
Self-complementary adeno-associated viral vector 9 (scAAV9) has been confirmed to be an efficient AAV serotype for gene transfer to the central nervous system (CNS). Neurotrophic factors have been considered to be therapeutic targets for amyotrophic lateral sclerosis (ALS). In the present study, we intramuscularly injected scAAV9 encoding human insulin-like growth factor 1 (hIGF1) into an hSOD1(G93A) ALS mouse model. We observed that scAAV9-hIGF1 significantly reduced the loss of motor neurons of the anterior horn in the lumbar spinal cord and delayed muscle atrophy in ALS mice...
December 19, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27992149/verantwortlicher-umgang-mit-antibiotika-notwendigkeit-der-antibiotikareduktion-in-der-aknetherapie
#9
Harald P M Gollnick, Jan Buer, Stefan Beissert, Cord Sunderkätter
Der übermäßige oder unkritische weltweite Einsatz von Antibiotika in der Medizin hat die Ausbreitung von Antibiotikaresistenzen beschleunigt. In einigen Bereichen sind viele Antibiotika bei bakteriellen Infektionen, die zuvor noch gut auf antibakterielle Wirkstoffe reagierten, mittlerweile wirkungslos geworden. Dermatologen/Venerologen setzten orale und topische Antibiotika bei der Behandlung von Acne vulgaris routinemäßig ein, obwohl Akne weder eine infektiöse Erkrankung ist noch alleine durch das Propionibacterium getriggert wird...
December 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/27992136/h%C3%A3-ufigkeit-und-einteilung-kutaner-manifestationen-bei-rheumatoider-arthritis
#10
Mirjana Ziemer, Anne-Katrin Müller, Gert Hein, Peter Oelzner, Peter Elsner
HINTERGRUND UND FRAGESTELLUNG: Hautveränderungen bei rheumatoider Arthritis (RA) sind nur in wenigen Studien an größeren Patientenkollektiven untersucht. Deshalb sollen hier die aktuelle Prävalenz und das Spektrum an Hautveränderungen bei RA unter Berücksichtigung von Krankheitsaktivitäts-Scores, Anti-CCP-Antikörpern sowie neueren medikamentösen Therapien erfasst werden. PATIENTEN UND METHODIK: Zwischen November 2006 und Juli 2007 wurden prospektiv 214 Patienten, die im Funktionsbereich Rheumatologie mit RA behandelt wurden, erfasst...
December 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/27965018/high-content-analysis-in-amyotrophic-lateral-sclerosis
#11
Federica Rinaldi, Dario Motti, Laura Ferraiuolo, Brian K Kaspar
Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by the progressive loss of motor neurons. Neurons, astrocytes, oligodendrocytes and microglial cells all undergo pathological modifications in the onset and progression of ALS. A number of genes involved in the etiopathology of the disease have been identified, but a complete understanding of the molecular mechanisms of ALS has yet to be determined. Currently, people affected by ALS have a life expectancy of only two to five years from diagnosis...
December 11, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27964824/pain-in-amyotrophic-lateral-sclerosis
#12
REVIEW
Adriano Chiò, Gabriele Mora, Giuseppe Lauria
Pain is a largely neglected symptom in patients with amyotrophic lateral sclerosis (ALS) although it is reported by most of these patients. It occurs at all stages of the disease and can be an onset symptom preceding motor dysfunction. Pain is correlated with a deterioration in patients' quality of life and increased prevalence of depression. In the later stages of ALS, pain can be severe enough to require increased use of sedative and analgesic drugs, and is among the events that predict clinical deterioration and death...
December 7, 2016: Lancet Neurology
https://www.readbyqxmd.com/read/27933416/positron-emission-tomography-in-amyotrophic-lateral-sclerosis-towards-targeting-of-molecular-pathological-hallmarks
#13
Stefanie M A Willekens, Donatienne Van Weehaeghe, Philip Van Damme, Koen Van Laere
During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD)...
December 8, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27922548/methylcobalamin-prevents-mutant-superoxide-dismutase-1-induced-motor-neuron-death-in-vitro
#14
Shunsuke Ito, Yukina Izumi, Tetsuhiro Niidome, Yuichi Ono
Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disorder that causes motor dysfunction. Treatments and drugs that slow progression of ALS have garnered great interest. In the present study, we show that the vitamin B12 analog methylcobalamin (MBL) effectively and dose dependently prevented embryonic stem cell-derived motor neuron death induced by cocultivation with astrocytes expressing mutant human superoxide dismutase-1 (G93A). Moreover, cotreatment of MBL with a conventional ALS drug, riluzole, further enhanced survival of motor neurons in this in-vitro ALS model...
January 18, 2017: Neuroreport
https://www.readbyqxmd.com/read/27916654/prion-like-mechanisms-and-potential-therapeutic-targets-in-neurodegenerative-disorders
#15
REVIEW
Masato Hasegawa, Takashi Nonaka, Masami Masuda-Suzukake
Prion-like propagation of abnormal intracytoplasmic proteins, which are the defining features of major neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), has been proposed. A growing body of evidence strongly suggests that abnormal tau, α-synuclein and TDP-43 have prion-like properties, convert the corresponding normal proteins into abnormal forms, and are transmitted from cell to cell, spreading throughout the brain. This idea is extremely important not only for understanding the pathogenesis and progression of these diseases, but also for the development of molecular therapies...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27892703/the-measurement-and-estimation-of-total-energy-expenditure-in-japanese-patients-with-als-a-doubly-labelled-water-method-study
#16
Toshio Shimizu, Kazuko Ishikawa-Takata, Akiko Sakata, Utako Nagaoka, Noriko Ichihara, Chiho Ishida, Yuki Nakayama, Tetsuo Komori, Masatoyo Nishizawa
Appropriate nutritional therapy has not been established for patients with amyotrophic lateral sclerosis (ALS). Our objective was to measure the total energy expenditure (TEE) and determine an equation to estimate the energy requirements for Japanese patients with ALS. Twenty-six Japanese patients with ALS participated in the study. The TEE was measured using the doubly labelled water (DLW) method for a 14-day period. Using a range of clinical parameters and multiple regression analyses, we determined an adequate equation to calculate TEE...
November 28, 2016: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/27873462/mitochondrial-dysfunction-and-biogenesis-in-neurodegenerative-diseases-pathogenesis-and-treatment
#17
REVIEW
Mojtaba Golpich, Elham Amini, Zahurin Mohamed, Raymond Azman Ali, Norlinah Mohamed Ibrahim, Abolhassan Ahmadiani
Neurodegenerative diseases are a heterogeneous group of disorders that are incurable and characterized by the progressive degeneration of the function and structure of the central nervous system (CNS) for reasons that are not yet understood. Neurodegeneration is the umbrella term for the progressive death of nerve cells and loss of brain tissue. Because of their high energy requirements, neurons are especially vulnerable to injury and death from dysfunctional mitochondria. Widespread damage to mitochondria causes cells to die because they can no longer produce enough energy...
January 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27869378/pathogenese-und-klinik-der-rosazea-als-schl%C3%A3-ssel-f%C3%A3-r-eine-symptomorientierte-therapie
#18
M Reinholz, T Ruzicka, M Steinhoff, M Schaller, U Gieler, H Schöfer, B Homey, P Lehmann, T A Luger
Rosazea ist eine häufige chronisch-entzündliche Hauterkrankung, die typischerweise bei Erwachsenen vorkommt und das Gesicht betrifft. Synonyme der Rosazea sind Acne rosacea, Kupferfinne, Rotfinne, Couperose und Rosacea. Die Erkrankung ist durch einen chronischen und schubartigen Verlauf gekennzeichnet und wird durch ein genetisch prädisponiertes, multifaktorielles Geschehen bedingt. Ein vermehrtes Auftreten wird bei hellem Hauttyp und positiver Familienanamnese verzeichnet. Die charakteristischen Rosazea-Symptome manifestieren sich vorwiegend, aber nicht ausschließlich zentrofazial, wobei Stirn, Nase, Kinn und die Wangen maßgeblich betroffen sind...
December 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/27869375/aktueller-stand-der-systemischen-rosazea-therapie
#19
M Schaller, H Schöfer, B Homey, U Gieler, P Lehmann, T A Luger, T Ruzicka, M Steinhoff
Basierend auf den Daten zahlreicher Studien sind orale Tetracycline - und hier insbesondere Doxycyclin als Tetracyclin der zweiten Generation - die Grundpfeiler der systemischen Rosazea-Therapie. Bisher ist dafür jedoch nur Doxycyclin 40 mg in antientzündlicher Dosierung mit veränderter Wirkstofffreisetzung zugelassen. Seit Einführung der Therapie mit Doxycyclin einmal täglich in nicht antibiotischer Dosierung wird die orale Therapie häufiger als Erstbehandlung bei mittelschwerer bis schwerer papulopustulöser Rosazea verschrieben...
December 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/27869373/rosazea-management-update-%C3%A3-ber-allgemeine-ma%C3%A3-nahmen-und-topische-therapieoptionen
#20
M Schaller, H Schöfer, B Homey, M Hofmann, U Gieler, P Lehmann, T A Luger, T Ruzicka, M Steinhoff
Obwohl bislang für die Rosazea keine kurative Therapie besteht, können verschiedene Optionen zur Behandlung der Symptome und zur Vorbeugung von Exazerbationen empfohlen werden. Neben Selbsthilfemaßnahme wie der Vermeidung von Triggerfaktoren und einer geeigneten Hautpflege sollte das Rosazea-Management bei Patienten mit erythematöser und leichter bis schwerer papulopustulöser Rosazea die Anwendung topischer Präparate als First-Line-Therapie umfassen. Da Überlappungen der charakteristischen Rosazea-Symptome im klinischen Alltag die Regel sind, sollte die medikamentöse Therapie auf die individuellen Symptome zugeschnitten werden; auch eine Kombinationstherapie kann erforderlich sein...
December 2016: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
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