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https://www.readbyqxmd.com/read/29149058/neurotrophic-and-neuroregenerative-effects-of-gh-igf1
#1
Vittorio Emanuele Bianchi, Vittorio Locatelli, Laura Rizzi
INTRODUCTION: Human neurodegenerative diseases increase progressively with age and present a high social and economic burden. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are both growth factors exerting trophic effects on neuronal regeneration in the central nervous system (CNS) and peripheral nervous system (PNS). GH and IGF-1 stimulate protein synthesis in neurons, glia, oligodendrocytes, and Schwann cells, and favor neuronal survival, inhibiting apoptosis. This study aims to evaluate the effect of GH and IGF-1 on neurons, and their possible therapeutic clinical applications on neuron regeneration in human subjects...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29121998/circulating-brain-enriched-micrornas-as-novel-biomarkers-for-detection-and-differentiation-of-neurodegenerative-diseases
#2
Kira S Sheinerman, Jon B Toledo, Vladimir G Tsivinsky, David Irwin, Murray Grossman, Daniel Weintraub, Howard I Hurtig, Alice Chen-Plotkin, David A Wolk, Leo F McCluskey, Lauren B Elman, John Q Trojanowski, Samuil R Umansky
BACKGROUND: Minimally invasive specific biomarkers of neurodegenerative diseases (NDs) would facilitate patient selection and disease progression monitoring. We describe the assessment of circulating brain-enriched microRNAs as potential biomarkers for Alzheimer's disease (AD), frontotemporal dementia (FTD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). METHODS: In this case-control study, the plasma samples were collected from 250 research participants with a clinical diagnosis of AD, FTD, PD, and ALS, as well as from age- and sex-matched control subjects (n = 50 for each group), recruited from 2003 to 2015 at the University of Pennsylvania Health System, including the Alzheimer's Disease Center, the Parkinson's Disease and Movement Disorders Center, the Frontotemporal Degeneration Center, and the Amyotrophic Lateral Sclerosis Clinic...
November 9, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/29116031/mirna-profiling-of-nurown%C3%A2-mesenchymal-stem-cells-secreting-neurotrophic-factors
#3
Yael Gothelf, Haggai Kaspi, Natalie Abramov, Revital Aricha
BACKGROUND: MSC-NTF cells are Mesenchymal Stromal Cells (MSC) induced to express high levels of neurotrophic factors (NTFs) using a culture-medium based approach. MSC-NTF cells have been successfully studied in clinical trials for Amyotrophic Lateral Sclerosis (ALS) patients. MicroRNAs (miRNA) are short non-coding RNA molecules that coordinate post-transcriptional regulation of multiple gene targets. The purpose of this study was to determine whether the miRNA profile could provide a tool for MSC-NTF cell characterization and to distinguish them from the matched MSC from which they are derived...
November 7, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29100791/monitoring-progression-of-amyotrophic-lateral-sclerosis-using-ultrasound-morpho-textural-muscle-biomarkers-a-pilot-study
#4
Jacinto J Martínez-Payá, José Ríos-Díaz, Francesc Medina-Mirapeix, Juan F Vázquez-Costa, María Elena Del Baño-Aledo
The need is increasing for progression biomarkers that allow the loss of motor neurons in amyotrophic lateral sclerosis (ALS) to be monitored in clinical trials. In this prospective longitudinal study, muscle thickness, echointensity, echovariation and gray level co-occurrence matrix textural features are examined as possible progression ultrasound biomarkers in ALS patients during a 5-mo follow-up period. We subjected 13 patients to 3 measurements for 20 wk. They showed a significant loss of muscle, an evident tendency to loss of thickness and increased echointensity and echovariation...
October 31, 2017: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/29095723/antiviral-treatment-of-severe-non-influenza-respiratory-virus-infection
#5
Nathan J Brendish, Tristan W Clark
PURPOSE OF REVIEW: Non-influenza respiratory virus infections are a frequent cause of severe acute respiratory infections, especially in infants, the elderly, and the immunocompromised. We review here the current treatment options for non-influenza respiratory viruses and promising candidate antiviral agents currently in development. RECENT FINDINGS: Small molecule antiviral agents active against respiratory syncytial virus (RSV), such as ALS-8176 and GS-5806, show considerable promise in challenge studies and are undergoing late-phase clinical trials in hospitalised adults and children...
December 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/29061611/effects-of-advanced-life-support-versus-basic-life-support-on-the-mortality-rates-of-patients-with-trauma-in-prehospital-settings-a-study-protocol-for-a-systematic-review-and-meta-analysis
#6
Yutaka Kondo, Tatsuma Fukuda, Ryo Uchimido, Toru Hifumi, Kei Hayashida
INTRODUCTION: Advanced life support (ALS) is thought to be associated with improved survival in prehospital trauma care when compared with basic life support (BLS). However, evidence on the benefits of prehospital ALS for patients with trauma is controversial. Therefore, we aim to clarify if ALS improves mortality in patients with trauma when compared with BLS by conducting a systematic review and meta-analysis of the recent literature. METHODS AND ANALYSIS: We will perform searches in PubMed, Embase and the Cochrane Central Register of Controlled Trials for published observational studies, controlled before-and-after studies, randomised controlled trials and other controlled trials conducted in humans and published until March 2017...
October 22, 2017: BMJ Open
https://www.readbyqxmd.com/read/29046475/evidence-for-mast-cells-contributing-to-neuromuscular-pathology-in-an-inherited-model-of-als
#7
Emiliano Trias, Sofía Ibarburu, Romina Barreto-Núñez, Valentina Varela, Ivan C Moura, Patrice Dubreuil, Olivier Hermine, Joseph S Beckman, Luis Barbeito
Evidence indicates that neuroinflammation contributes to motor neuron degeneration in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease leading to progressive muscular paralysis. However, it remains elusive whether inflammatory cells can interact with degenerating distal motor axons, influencing the progressive denervation of neuromuscular junctions (NMJs). By analyzing the muscle extensor digitorum longus (EDL) following paralysis onset in the SOD1G93A rat model, we have observed a massive infiltration and degranulation of mast cells, starting after paralysis onset and correlating with progressive NMJ denervation...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29033893/shortcomings-in-the-current-amyotrophic-lateral-sclerosis-trials-and-potential-solutions-for-improvement
#8
REVIEW
Nakul Katyal, Raghav Govindarajan
Amyotrophic lateral sclerosis (ALS) is a clinically progressive neurodegenerative syndrome predominantly affecting motor neurons and their associated tracts. Riluzole and edaravone are the only FDA certified drugs for treating ALS. Over the past two decades, almost all clinical trials aiming to develop a successful therapeutic strategy for this disease have failed. Genetic complexity, inadequate animal models, poor clinical trial design, lack of sensitive biomarkers, and diagnostic delays are some of the potential reasons limiting any significant development in ALS clinical trials...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29031901/als-and-ftd-insights-into-the-disease-mechanisms-and-therapeutic-targets
#9
Rajka M Liscic
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders, related by signs of deteriorating motor and cognitive functions, and short survival. The causes are still largely unknown and no effective treatment currently exists. It has been shown that FTLD may coexist with ALS. The overlap between ALS and frontotemporal dementia (FTD), the clinical syndrome associated with FTLD, occurs at clinical, genetic, and pathological levels. The hallmark proteins of the pathognomonic inclusions are SOD-1, TDP-43 or FUS, rarely the disease is caused by mutations in the respective genes...
October 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28993751/immune-modulation-in-the-treatment-of-amyotrophic-lateral-sclerosis-a-review-of-clinical-trials
#10
REVIEW
Syed I Khalid, Leonel Ampie, Ryan Kelly, Shafeeq S Ladha, Christopher Dardis
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of several potential immune-modulating therapies...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28982219/mechanical-ventilation-for-amyotrophic-lateral-sclerosis-motor-neuron-disease
#11
REVIEW
Aleksandar Radunovic, Djillali Annane, Muhammad K Rafiq, Ruth Brassington, Naveed Mustfa
BACKGROUND: Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a fatal neurodegenerative disease. Neuromuscular respiratory failure is the most common cause of death, which usually occurs within two to five years of the disease onset. Supporting respiratory function with mechanical ventilation may improve survival and quality of life. This is the second update of a review first published in 2009. OBJECTIVES: To assess the effects of mechanical ventilation (tracheostomy-assisted ventilation and non-invasive ventilation (NIV)) on survival, functional measures of disease progression, and quality of life in ALS, and to evaluate adverse events related to the intervention...
October 6, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28978660/meta-analysis-of-pharmacogenetic-interactions-in-amyotrophic-lateral-sclerosis-clinical-trials
#12
REVIEW
Ruben P A van Eijk, Ashley R Jones, William Sproviero, Aleksey Shatunov, Pamela J Shaw, P Nigel Leigh, Carolyn A Young, Christopher E Shaw, Gabriele Mora, Jessica Mandrioli, Giuseppe Borghero, Paolo Volanti, Frank P Diekstra, Wouter van Rheenen, Esther Verstraete, Marinus J C Eijkemans, Jan H Veldink, Adriano Chio, Ammar Al-Chalabi, Leonard H van den Berg, Michael A van Es
OBJECTIVE: To assess whether genetic subgroups in recent amyotrophic lateral sclerosis (ALS) trials responded to treatment with lithium carbonate, but that the treatment effect was lost in a large cohort of nonresponders. METHODS: Individual participant data were obtained from 3 randomized trials investigating the efficacy of lithium carbonate. We matched clinical data with data regarding the UNC13A and C9orf72 genotype. Our primary outcome was survival at 12 months...
October 31, 2017: Neurology
https://www.readbyqxmd.com/read/28943839/cellular-chaperones-as-therapeutic-targets-in-als-to-restore-protein-homeostasis-and-improve-cellular-function
#13
REVIEW
Bernadett Kalmar, Linda Greensmith
Heat shock proteins (Hsps) are ubiquitously expressed chaperone proteins that enable cells to cope with environmental stresses that cause misfolding and denaturation of proteins. With aging this protein quality control machinery becomes less effective, reducing the ability of cells to cope with damaging environmental stresses and disease-causing mutations. In neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS), such mutations are known to result in protein misfolding, which in turn results in the formation of intracellular aggregates cellular dysfunction and eventual neuronal death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28933017/present-uses-future-applications-and-technical-underpinnings-of-electrical-impedance-myography
#14
REVIEW
Benjamin Sanchez, Seward B Rutkove
PURPOSE OF REVIEW: In this article, we provide an overview of electrical impedance myography (EIM), including its technical and theoretical basis, a summary of its varied applications, and ongoing developments. RECENT FINDINGS: EIM has been used as a disease severity biomarker in a variety of disorders affecting the muscle, ranging from amyotrophic lateral sclerosis (ALS) to muscular dystrophies to disuse atrophy due to the weightlessness of space. In ALS, studies have demonstrated that major reductions in sample size in clinical trials can be achieved...
September 20, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28911903/the-vaccines-and-antibodies-associated-with-als3p-for-treatment-of-candida-albicans-infections
#15
REVIEW
Xue Sui, Lan Yan, Yuan-Ying Jiang
Candida albicans is the most common fungal microorganism in healthy individuals, as well as the cause of high mortality infections in high-risk hosts such as immunocompromised patients. Antifungal vaccines and monoclonal antibodies useful for active or passive immunizations have recently generated considerable excitement for the treatment of fungal infections. The cell wall proteins of C. albicans, which are crucial for virulence and pathogenicity, are attractive target antigens. Als3p, a member of the C. albicans agglutinin-like sequence (ALS) family, is a hyphal-specific glycophosphatidylinositol cell wall protein that plays a key role in the interaction with host cells...
September 11, 2017: Vaccine
https://www.readbyqxmd.com/read/28872919/a-safety-analysis-of-edaravone-mci-186-during-the-first-six-cycles-24-weeks-of-amyotrophic-lateral-sclerosis-als-therapy-from-the-double-blind-period-in-three-randomized-placebo-controlled-studies
#16
Alexander Kalin, Elvia Medina-Paraiso, Kaoru Ishizaki, Alex Kim, Yannong Zhang, Takanori Saita, Masahiko Wasaki
BACKGROUND: There continues to be a need for new therapies to treat ALS. OBJECTIVE: Provide an overview of safety for edaravone in ALS patients during the first six cycles of treatment. METHODS: Analysis was based on three randomised, placebo-controlled clinical trials. Endpoints included treatment-emergent adverse events (TEAEs), including AEs leading to discontinuation, serious adverse events (SAEs), and deaths. RESULTS: The analysis included a total of 368 patients (184 in the edaravone group and placebo group, respectively)...
October 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28872912/an-assessment-of-treatment-guidelines-clinical-practices-demographics-and-progression-of-disease-among-patients-with-amyotrophic-lateral-sclerosis-in-japan-the-united-states-and-europe
#17
Koji Takei, Kikumi Tsuda, Fumihiro Takahashi, Manabu Hirai, Joseph Palumbo
BACKGROUND: There is an increasing clinical research focus on neuroprotective agents in amyotrophic lateral sclerosis (ALS). However, it is unclear how generalisable clinical study trial results are between different countries and regions. OBJECTIVE: To assess similarities and differences in clinical practice and treatment guidelines for ALS, and also to compare the demographics and rate of progression of disease in patients with ALS enrolled in clinical trials in Japan, the US, and Europe...
October 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28872908/pharmacokinetic-profile-of-edaravone-a-comparison-between-japanese-and-caucasian-populations
#18
Yoshinobu Nakamaru, Shuji Kinoshita, Atsuhiro Kawaguchi, Koji Takei, Joseph Palumbo, Masayuki Suzuki
BACKGROUND: Amyotrophic lateral sclerosis (ALS) affects persons of all races, and there continues to be a need for effective therapies to treat the disease. OBJECTIVE: To compare the pharmacokinetics (PK) of edaravone between Japanese and Caucasian populations. METHODS: Data from five PK studies among Japanese and Caucasian healthy volunteers were pooled and evaluated. In population PK (PPK) modelling, compartment models and other models with linear elimination were evaluated for appropriateness...
October 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28869393/ethics-of-clinical-research-in-patients-with-als-is-there-a-risk-of-exploitation
#19
Carmel Armon
Amyotrophic lateral sclerosis is the most common degenerative disease of the motor neuron network. Due to its inevitably fatal outcome, numerous attempts have been made to ameliorate its course. The emergence of every new technology has spurred research to see if it might benefit patients with ALS (PALS). This paper suggests a detailed road map to be followed when performing clinical research in PALS to satisfy the ethics requirements of the Declaration of Helsinki, expressed using the terminology of Beauchamp and Childress...
September 4, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28869278/cerebral-near-infrared-spectroscopy-monitoring-for-prevention-of-brain-injury-in-very-preterm-infants
#20
REVIEW
Simon Hyttel-Sorensen, Gorm Greisen, Bodil Als-Nielsen, Christian Gluud
BACKGROUND: Cerebral injury and long-term neurodevelopmental impairment is common in extremely preterm infants. Cerebral near-infrared spectroscopy (NIRS) enables continuous estimation of cerebral oxygenation. This diagnostic method coupled with appropriate interventions if NIRS is out of normal range (that is cerebral oxygenation within the 55% to 85% range) may offer benefits without causing more harms. Therefore, NIRS coupled with appropriate responses to abnormal findings on NIRS needs assessment in a systematic review of randomised clinical trials and quasi-randomised studies...
September 4, 2017: Cochrane Database of Systematic Reviews
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