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https://www.readbyqxmd.com/read/28302022/glial-cell-a-potential-target-for-cellular-and-drug-based-therapy-in-various-cns-diseases
#1
Shakeeb Ahmed, Yasmin Sultana, Azka Gull, Tahir Khuroo, Mohd Aqil
Glial cells are integrated part of neurovascular unit of blood brain barrier (BBB). They undergo mitosis and mainly classified as astrocytes, oligodendrocytes, microglia, ependymal cells and nerve glial antigen 2 cells. Being a most versatile glial cell, astrocytes provide structural support to neurons, maintain brain homeostasis, take part in neuronal communication, and perform some housekeeping functions. Oligodendrocytes myelinate the neuronal axons for proper transmission of nerve impulse and microglia are brain immune cells...
March 16, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28293476/evaluating-the-levels-of-csf-and-serum-factors-in-als
#2
Jie Guo, Xuan Yang, Lina Gao, Dawei Zang
OBJECTIVES: The aim of this study was to identify CSF and serum factors as biomarkers that may aid in distinguishing ALS patients from control subjects and predicting ALS progression as well as prognosis. METHODS: Serum and CSF samples from 105 patients with ALS and 56 control subjects were analyzed for 13 factors using ELISA. The revised ALS functional rating scale (ALSFRS-r) was used to evaluate the overall functional status of ALS patients, and we also followed up with ALS patients either by phone or with clinic visits for five years after enrollment in this study...
March 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28277881/drugs-in-clinical-development-for-the-treatment-of-amyotrophic-lateral-sclerosis
#3
Ana Martinez, Maria Del Valle Palomo Ruiz, Daniel I Perez, Carmen Gil
Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron progressive disorder for which no treatment exists to date. However, there are other investigational drugs and therapies currently under clinical development may offer hope in the near future. Areas covered: We have reviewed all the ALS ongoing clin ical trials (until November 2016) and collected in Clinicaltrials.gov or EudraCT. We have described them in a comprehensive way and have grouped them in the following sections: biomarkers, biological therapies, cell therapy, drug repurposing and new drugs...
March 6, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28267691/vorapaxar-and-amyotrophic-lateral-sclerosis-coincidence-or-adverse-association
#4
REVIEW
Victor L Serebruany, Seth D Fortmann, Daniel F Hanley, Moo Hyun Kim
BACKGROUND: Vorapaxar, a novel antiplatelet thrombin PAR-1 inhibitor, is currently approved for post myocardial infarction and peripheral artery disease indications with concomitant use of clopidogrel and/or aspirin. The vorapaxar safety profile was acceptable. However, aside from heightened bleeding risks, excesses of solid cancers and diplopia, there were more amyotrophic lateral sclerosis (ALS) diagnoses after vorapaxar. STUDY QUESTION: To assess the Food and Drug Administration (FDA) reviews on the potential association of vorapaxar with ALS...
March 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/28265751/peripheral-nerve-diffusion-tensor-imaging-as-a-measure-of-disease-progression-in-als
#5
Neil G Simon, Jim Lagopoulos, Sita Paling, Casey Pfluger, Susanna B Park, James Howells, Thomas Gallagher, Michel Kliot, Robert D Henderson, Steve Vucic, Matthew C Kiernan
Clinical trial design in amyotrophic lateral sclerosis (ALS) remains hampered by a lack of reliable and sensitive biomarkers of disease progression. The present study evaluated peripheral nerve diffusion tensor imaging (DTI) as a surrogate marker of axonal degeneration in ALS. Longitudinal studies were undertaken in 21 ALS patients studied at 0 and 3 months, and 19 patients at 0, 3 and 6 months, with results compared to 13 age-matched controls. Imaging metrics were correlated across a range of functional assessments including amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R), lower limb muscle strength (Medical Research Council sum score, MRCSS-LL), compound muscle action potential amplitudes and motor unit number estimation (MUNE)...
March 6, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28242130/kennedy-s-disease-1234-scale-preliminary-design-and-test
#6
Ming Lu, Haixiao Guo, Dongsheng Fan
Kennedy's disease (KD), also known as spinal and bulbar muscular atrophy (SBMA), is a rare x-linked genetic disorder which is characterized by muscle weakness and atrophy. In previous clinical trials, KD patients had been assessed using the ALSFRS scale, which was specifically designed for ALS patients. However, the progression of KD is very slow, and thus, the ALSFRS does not accurately reflect changes in the clinical condition of KD patient. Here, we developed the KD 1234 scale which designed specially for KD...
February 24, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28241758/clinical-trials-from-the-patient-perspective-survey-in-an-online-patient-community
#7
Pronabesh DasMahapatra, Priya Raja, Jeremy Gilbert, Paul Wicks
BACKGROUND: Developing new medicines relies on the successful conduct of clinical trials. As trial protocols become more arduous, it becomes harder to recruit and retain patient volunteers, although recent efforts such as OMERACT and I-SPY2 show that partnering with patients can be beneficial. We sought to describe drivers and barriers to trial participation, as well as condition-specific trial preferences. METHODS: An online survey was fielded via the patient-powered research network PatientsLikeMe to 1,621 members living with nine selected chronic health conditions...
February 27, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28236105/selection-and-prioritization-of-candidate-drug-targets-for-amyotrophic-lateral-sclerosis-through-a-meta-analysis-approach
#8
Giovanna Morello, Antonio Gianmaria Spampinato, Francesca Luisa Conforti, Velia D'Agata, Sebastiano Cavallaro
Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. Although several compounds have shown promising results in preclinical studies, their translation into clinical trials has failed. This clinical failure is likely due to the inadequacy of the animal models that do not sufficiently reflect the human disease. Therefore, it is important to optimize drug target selection by identifying those that overlap in human and mouse pathology. We have recently characterized the transcriptional profiles of motor cortex samples from sporadic ALS (SALS) patients and differentiated these into two subgroups based on differentially expressed genes, which encode 70 potential therapeutic targets...
February 24, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28229508/meditation-training-for-people-with-amyotrophic-lateral-sclerosis-a-randomized-clinical-trial
#9
F Pagnini, A Marconi, A Tagliaferri, G M Manzoni, R Gatto, V Fabiani, G Gragnano, G Rossi, E Volpato, P Banfi, A Palmieri, F Graziano, G Castelnuovo, M Corbo, E Molinari, N Riva, V Sansone, C Lunetta
BACKGROUND AND PURPOSE: Studies investigating psychological interventions for the promotion of well-being in people with amyotrophic lateral sclerosis (ALS) are lacking. The purpose of the current study was to examine the use of an ALS-specific mindfulness-based intervention for improving quality of life in this population. METHODS: A randomized, open-label and controlled clinical trial was conducted on the efficacy of an ALS-specific meditation programme in promoting quality of life...
February 23, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28197175/can-cannabinoids-be-a-potential-therapeutic-tool-in-amyotrophic-lateral-sclerosis
#10
REVIEW
Sabrina Giacoppo, Emanuela Mazzon
Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28105588/nogo-a-antibodies-for-progressive-multiple-sclerosis
#11
Benjamin V Ineichen, Patricia S Plattner, Nicolas Good, Roland Martin, Michael Linnebank, Martin E Schwab
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair...
January 19, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28088365/stem-cells-for-als-an-overview-of-possible-therapeutic-approaches
#12
REVIEW
Joanna Czarzasta, Aleksandra Habich, Tomasz Siwek, Adam Czapliński, Wojciech Maksymowicz, Joanna Wojtkiewicz
Amyotrophic lateral sclerosis (ALS) is an unusual, fatal, neurodegenerative disorder leading to the loss of motor neurons. After diagnosis, the average lifespan ranges from 3 to 5 years, and death usually results from respiratory failure. Although the pathogenesis of ALS remains unclear, multiple factors are thought to contribute to the progression of ALS, such as network interactions between genes, environmental exposure, impaired molecular pathways and many others. The neuroprotective properties of neural stem cells (NSCs) and the paracrine signaling of mesenchymal stem cells (MSCs) have been examined in multiple pre-clinical trials of ALS with promising results...
April 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28072907/symptomatic-treatments-for-amyotrophic-lateral-sclerosis-motor-neuron-disease
#13
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/28070747/enhanced-bulbar-function-in-amyotrophic-lateral-sclerosis-the-nuedexta-treatment-trial
#14
Richard Smith, Erik Pioro, Kathleen Myers, Michael Sirdofsky, Kimberly Goslin, Gregg Meekins, Hong Yu, James Wymer, Merit Cudkowicz, Eric A Macklin, David Schoenfeld, Gary Pattee
The goal of this randomized, blinded, crossover clinical trial was to determine whether Nuedexta (dextromethorphan and quinidine) enhanced speech, swallowing, and salivation in patients with ALS. Sixty patients with amyotrophic lateral sclerosis (ALS) received either Nuedexta or placebo for 28 to 30 days, followed by a 10 to 15-day washout period. Subsequently, patients were switched to the opposite treatment arm for the remaining days of the trial. The primary endpoint was a reduction in the self-report Center for Neurologic Study Bulbar Function Scale (CNS-BFS) score...
January 9, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28067943/gamma-aminobutyric-acid-gaba-modulators-for-amyotrophic-lateral-sclerosis-motor-neuron-disease
#15
REVIEW
Andrea Diana, Rita Pillai, Paolo Bongioanni, Aidan G O'Keeffe, Robert G Miller, Dan H Moore
BACKGROUND: Imbalance of gamma aminobutyric acid (GABA) and related modulators has been implicated as an important factor in the pathogenesis of amyotrophic lateral sclerosis (ALS), which is also known as motor neuron disease (MND). In this context, the role and mechanism of action of gabapentin and baclofen have been extensively investigated, although with conflicting results. This is the first systematic review to assess clinical trials of GABA modulators for the treatment of ALS. OBJECTIVES: To examine the efficacy of gabapentin, baclofen, or other GABA modulators in delaying the progression of ALS, and to evaluate adverse effects of these interventions SEARCH METHODS: On 16 August 2016, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL Plus, AMED, and LILACS...
January 9, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28054828/comparison-of-the-king-s-and-mitos-staging-systems-for-als
#16
Ton Fang, Ahmad Al Khleifat, Daniel R Stahl, Claudia Lazo La Torre, Caroline Murphy, Carolyn Young, Pamela J Shaw, P Nigel Leigh, Ammar Al-Chalabi
OBJECTIVE: To investigate and compare two ALS staging systems, King's clinical staging and Milano-Torino (MiToS) functional staging, using data from the LiCALS phase III clinical trial (EudraCT 2008-006891-31). METHODS: Disease stage was derived retrospectively for each system from the ALS Functional Rating Scale-Revised subscores using standard methods. The two staging methods were then compared for timing of stages using box plots, correspondence using chi-square tests, agreement using a linearly weighted kappa coefficient and concordance using Spearman's rank correlation...
January 5, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28009454/direct-estimation-for-adaptive-treatment-length-policies-methods-and-application-to-evaluating-the-effect-of-delayed-peg-insertion
#17
Xin Lu, Brent A Johnson
Dysphagia is a primary cause of death among patients diagnosed with amyotrophic lateral sclerosis (ALS), and percutaneous endoscopic gastrostomy (PEG) is a procedure to insert a tube into the stomach to assist or replace oral feeding. It is believed that PEG is beneficial and, generally, earlier insertion is preferable to later. However, gathering clinical evidence to support these beliefs on the use and timing of PEG is challenging because controlled clinical trials are not feasible and clinical endpoints are confounded with PEG in observational data...
December 23, 2016: Biometrics
https://www.readbyqxmd.com/read/27999880/-pathomechanisms-and-clinical-aspects-of-frontotemporal-lobar-degeneration
#18
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...
February 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/27983884/extra-motor-abnormalities-in-amyotrophic-lateral-sclerosis-another-layer-of-heterogeneity
#19
P A McCombe, N R Wray, R D Henderson
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease defined by the presence of muscle weakness. The motor features of disease are heterogeneous in site of onset and progression. There are also extra-motor features in some patients. The genetic basis for extra-motor features is uncertain. The heterogeneity of ALS is an issue for clinical trials. Areas covered: This paper reviews the range and prevalence of extra-motor features associated with ALS, and highlights the current information about genetic associations with extra-motor features...
January 3, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27964824/pain-in-amyotrophic-lateral-sclerosis
#20
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...
February 2017: Lancet Neurology
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