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https://www.readbyqxmd.com/read/29453787/a-phase-ii-trial-of-riluzole-an-antagonist-of-metabotropic-glutamate-receptor-1-grm1-signaling-in-patients-with-advanced-melanoma
#1
Janice M Mehnert, Ann W Silk, Yu Wen, J H Lee, Liesel Dudek, Byeong-Seon Jeong, Jiadong Li, Jason M Schenkel, Evita Sadimin, Michael Kane, Hongxia Lin, Weichung J Shih, Andrew Zloza, Suzie Chen, James S Goydos
Studies demonstrate that GRM, expressed by >60% of human melanomas, may be a therapeutic target. We performed a phase II trial of 100 mg po bid of riluzole, an inhibitor of GRM1 signaling, in patients with advanced melanoma with the primary endpoint of response rate. Thirteen patients with GRM1-positive tumors were enrolled. No objective responses were observed and accrual was stopped. Stable disease was noted in 6 (46%) patients, with 1 patient on study for 42 weeks. Riluzole was well-tolerated, with fatigue (62%) as the most common adverse event...
February 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29440566/comprehensive-systematic-review-summary-treatment-of-cerebellar-motor-dysfunction-and-ataxia-report-of-the-guideline-development-dissemination-and-implementation-subcommittee-of-the-american-academy-of-neurology
#2
Theresa A Zesiewicz, George Wilmot, Sheng-Han Kuo, Susan Perlman, Patricia E Greenstein, Sarah H Ying, Tetsuo Ashizawa, S H Subramony, Jeremy D Schmahmann, K P Figueroa, Hidehiro Mizusawa, Ludger Schöls, Jessica D Shaw, Richard M Dubinsky, Melissa J Armstrong, Gary S Gronseth, Kelly L Sullivan
OBJECTIVE: To systematically review evidence regarding ataxia treatment. METHODS: A comprehensive systematic review was performed according to American Academy of Neurology methodology. CONCLUSIONS: For patients with episodic ataxia type 2, 4-aminopyridine 15 mg/d probably reduces ataxia attack frequency over 3 months (1 Class I study). For patients with ataxia of mixed etiology, riluzole probably improves ataxia signs at 8 weeks (1 Class I study)...
February 9, 2018: Neurology
https://www.readbyqxmd.com/read/29405033/therapy-in-amyotrophic-lateral-sclerosis-als-an-unexpected-evolving-scenario
#3
Vincenzo Silani
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease resulting in increasing disability, being uniformly fatal. Since its approval in the 1990s, riluzole remained for long time the unique treatment, offering modest survival benefit. Most recently a second drug has been approved by the US Food and Drug Administration for treatment of ALS: edaravone. Significant advances have been made in the symptomatic management of the disease but more effective drug therapy targeting disease progression is still dreadfully needed, the success appearing almost a miracle...
December 1, 2017: Archives Italiennes de Biologie
https://www.readbyqxmd.com/read/29404735/riluzole-and-other-prognostic-factors-in-als-a-population-based-registry-study-in-italy
#4
Jessica Mandrioli, Sara Angela Malerba, Ettore Beghi, Nicola Fini, Antonio Fasano, Elisabetta Zucchi, Silvia De Pasqua, Carlo Guidi, Emilio Terlizzi, Elisabetta Sette, Alessandro Ravasio, Mario Casmiro, Fabrizio Salvi, Rocco Liguori, Lucia Zinno, Yasmin Handouk, Romana Rizzi, Annamaria Borghi, Rita Rinaldi, Doriana Medici, Mario Santangelo, Enrico Granieri, Vittoria Mussuto, Marina Aiello, Salvatore Ferro, Marco Vinceti
OBJECTIVE: In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS cases in Emilia Romagna Region (ERR), Italy. METHODS: A registry for ALS has been collecting all incident cases in ERR since 2009. Detailed clinical data from all patients diagnosed with ALS between 1.1.2009 and 31.12.2014 have been analyzed for this study, with last follow up date set at 31...
February 5, 2018: Journal of Neurology
https://www.readbyqxmd.com/read/29399045/disease-modifying-and-symptomatic-treatment-of-amyotrophic-lateral-sclerosis
#5
REVIEW
Johannes Dorst, Albert C Ludolph, Annemarie Huebers
In this review, we summarize the most important recent developments in the treatment of amyotrophic lateral sclerosis (ALS). In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results. Therefore, riluzole remains the only directly disease-modifying drug. In addition, we discuss antisense oligonucleotides (ASOs) as a new and potentially causal treatment option. Progress in symptomatic treatments has been more important...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29396541/tdp-43-self-interaction-is-modulated-by-redox-active-compounds-auranofin-chelerythrine-and-riluzole
#6
Moritz Oberstadt, Jens Stieler, David Larbi Simpong, Ute Römuß, Nicole Urban, Michael Schaefer, Thomas Arendt, Max Holzer
Amyotrophic lateral sclerosis (ALS) represents a fatal neurodegenerative disease, which is characterized by a rapid loss of lower and upper motor neurons. As a major neuropathological hallmark, protein aggregates containing the Transactivating Response Region (TAR) DNA Binding Protein (TDP-43) are detectable in about 95% of sporadic ALS patients. TDP-43 interacts with itself physiologically to form liquid droplets, which may progress to pathological aggregates. In this study, we established the NanoBit luciferase complementation assay to measure TDP-43 self-interaction and found the fusion of the split luciferase subunits to the N-terminus of the protein as the strongest interacting partners...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29379292/adherence-to-riluzole-in-patients-with-amyotrophic-lateral-sclerosis-an-observational-study
#7
Alessandro Introna, Eustachio D'Errico, Boris Modugno, Antonio Scarafino, Angela Fraddosio, Eugenio Distaso, Irene Tempesta, Antonella Mastronardi, Isabella Laura Simone
Objective: Riluzole is the first drug approved to treat amyotrophic lateral sclerosis (ALS). Recently, an oral suspension (OS) of riluzole was made available. Thus, the aim of our study was to evaluate the adherence to 2 formulations of riluzole in patients with ALS. Patients and methods: We enrolled 45 consecutive patients with ALS. At disease diagnosis, riluzole was prescribed in 2 different formulations depending on the severity of dysphagia (27/45 patients received tablets and 18/45 patients received OS)...
2018: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29367439/randomized-double-blind-placebo-controlled-trial-of-arimoclomol-in-rapidly-progressive-sod1-als
#8
Michael Benatar, Joanne Wuu, Peter M Andersen, Nazem Atassi, William David, Merit Cudkowicz, David Schoenfeld
OBJECTIVE: To examine the safety and tolerability as well as the preliminary efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent protein folding, in patients with rapidly progressive SOD1 amyotrophic lateral sclerosis (ALS). METHODS: This was a double-blind, placebo-controlled trial in which patients with rapidly progressive SOD1-mutant ALS were randomized 1:1 to receive arimoclomol 200 mg tid or matching placebo for up to 12 months. Study procedures were performed using a mix of in-person and remote assessments...
January 24, 2018: Neurology
https://www.readbyqxmd.com/read/29357349/knockdown-of-wfs1-a-fly-homolog-of-wolfram-syndrome-1-in-the-nervous-system-increases-susceptibility-to-age-and-stress-induced-neuronal-dysfunction-and-degeneration-in-drosophila
#9
Yasufumi Sakakibara, Michiko Sekiya, Naoki Fujisaki, Xiuming Quan, Koichi M Iijima
Wolfram syndrome (WS), caused by loss-of-function mutations in the Wolfram syndrome 1 gene (WFS1), is characterized by juvenile-onset diabetes mellitus, bilateral optic atrophy, and a wide spectrum of neurological and psychiatric manifestations. WFS1 encodes an endoplasmic reticulum (ER)-resident transmembrane protein, and mutations in this gene lead to pancreatic β-cell death induced by high levels of ER stress. However, the mechanisms underlying neurodegeneration caused by WFS1 deficiency remain elusive...
January 22, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29356625/multi-omics-for-biomarker-discovery-and-target-validation-in-biofluids-for-amyotrophic-lateral-sclerosis-diagnosis
#10
Konstantinos Mitropoulos, Theodora Katsila, George P Patrinos, Georgios Pampalakis
Amyotrophic lateral sclerosis (ALS) is a rare but usually fatal neurodegenerative disease characterized by motor neuron degeneration in the brain and the spinal cord. Two forms are recognized, the familial that accounts for 5-10% and the sporadic that accounts for the rest. New studies suggest that ALS is a highly heterogeneous disease, and this diversity is a major reason for the lack of successful therapeutic treatments. Indeed, only two drugs (riluzole and edaravone) have been approved that provide a limited improvement in the quality of life...
January 2018: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/29352425/safety-and-efficacy-of-nanocurcumin-as-add-on-therapy-to-riluzole-in-patients-with-amyotrophic-lateral-sclerosis-a-pilot-randomized-clinical-trial
#11
Mona Ahmadi, Elmira Agah, Shahriar Nafissi, Mahmoud Reza Jaafari, Mohammad Hossein Harirchian, Payam Sarraf, Sara Faghihi-Kashani, Seyed Jalal Hosseini, Abdolreza Ghoreishi, Vajiheh Aghamollaii, Mostafa Hosseini, Abbas Tafakhori
The objective of present study was to assess the safety and efficacy of nanocurcumin as an anti-inflammatory and antioxidant agent in adults with amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind, randomized, placebo-controlled trial at a neurological referral center in Iran. Eligible patients with a definite or probable ALS diagnosis were randomly assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio. A computerized random number generator was used to prepare the randomization list...
January 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29341886/regulation-of-hsf1-protein-stabilization-an-updated-review
#12
REVIEW
Chao Huang, Jingjing Wu, Li Xu, Jili Wang, Zhuo Chen, Rongrong Yang
Heat shock factor 1 (HSF1) is a transcriptional factor that determines the efficiency of heat shock responses (HSRs) in the cell. Given its function has been extensively studied in recent years, HSF1 is considered a potential target for the treatment of disorders associated with protein aggregation. The activity of HSF1 is traditionally regulated at the transcriptional level in which the transactivation domain of HSF1 is modified by extensive array of pos-translational modifications, such as phosphorylation, sumoylation, and acetylation...
January 13, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29339770/reversing-cocaine-induced-adaptations-and-reducing-relapse-an-opportunity-for-repurposing-riluzole
#13
Joseph J Ziminski, Eisuke Koya
No abstract text is available yet for this article.
January 17, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29295647/prophylactic-riluzole-attenuates-oxidative-stress-damage-in-spinal-cord-distraction
#14
Eileen Nicole Shimizu, Jennifer L Seifert, Kevin J Johnson, Mario Romero-Ortega
Spinal cord injury (SCI) without radiographic abnormalities (SCIWORA) presents a significant challenge due the loss of function despite an apparent normal anatomy. The cause of dysfunction is not understood and specific treatment options are lacking. Some scoliosis corrective surgeries result in SCIWORA, where stretching of the spinal cord can lead to vascular compromise and hypoxia. This procedure allows for the implantation of neuroprotective strategies designed to prevent iatrogenic SCI. We utilized a model of atraumatic SCI to evaluate the efficacy of the sodium channel blocker Riluzole, as a prophylactic neuroprotectant...
January 2, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29290040/mechanism-of-neuroprotection-against-experimental-spinal-cord-injury-by-riluzole-or-methylprednisolone
#15
Cynthia Sámano, Andrea Nistri
Any spinal cord injury carries the potential for persistent disability affecting motor, sensory and autonomic functions. To prevent this outcome, it is highly desirable to block a chain of deleterious reactions developing in the spinal areas immediately around the primary lesion. Thus, early timing of pharmacological neuroprotection should be one major strategy whose impact may be first studied with preclinical models. Using a simple in vitro model of the rat spinal cord it is possible to mimic pathological processes like excitotoxicity that damages neurons because of excessive glutamate receptor activation due to injury, or hypoxic/dysmetabolic insult that preferentially affects glia following vascular dysfunction...
December 30, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29228563/riluzole-a-potential-therapeutic-intervention-in-human-brain-tumor-stem-like-cells
#16
Swetlana Sperling, Thiha Aung, Sabine Martin, Veit Rohde, Milena Ninkovic
A small subpopulation of tumor stem-like cells has the capacity to initiate tumors and mediate radio- and chemoresistance in diverse cancers hence also in glioblastoma (GBM). It has been reported that this capacity of tumor initiation in the brain is mainly dependent on the body's nutrient supply. This population of so-called brain tumor initiating or brain tumor stem-like cells (BTSCs) is able to extract nutrients like glucose with a higher affinity. Riluzole, a drug approved for treating amyotrophic lateral sclerosis (ALS), was reported to possess anticancer properties, affecting the glutamate metabolism...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226728/the-efficacy-and-safety-of-riluzole-for-neurodegenerative-movement-disorders-a-systematic-review-with-meta-analysis
#17
Jia Liu, Lu-Ning Wang
Neurodegenerative movement disorders mainly include Parkinson's disease, atypical parkinsonisms, Huntington disease, and hereditary ataxia. Riluzole is the only drug approved by the US Food and Drug Administration for amyotrophic lateral sclerosis. The neuroprotective effects of riluzole have been observed in experimental models of neurodegenerative movement disorders. In this paper, we aimed to systematically analyze the efficacy and safety of riluzole for patients with neurodegenerative movement disorder...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29225045/post-reexposure-administration-of-riluzole-attenuates-the-reconsolidation-of-conditioned-fear-memory-in-rats
#18
Kie Akagi, Misa Yamada, Akiyoshi Saitoh, Jun-Ichiro Oka, Mitsuhiko Yamada
Recently, we demonstrated that riluzole, which has been shown to block the glutamatergic system, facilitates fear extinction in rats. Here, we undertook experiments on contextual fear conditioning to clarify the actions of riluzole on the reconsolidation of fear memory in rats. We used the fast-acting benzodiazepine midazolam as a reconsolidation-inhibiting control drug. We demonstrated that riluzole (3 mg/kg) and midazolam (1 mg/kg) impaired the reconsolidation of contextual fear memory. Results from spontaneous recovery experiments also suggested that riluzole attenuated reconsolidation...
December 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29221425/riluzole-does-not-improve-lifespan-or-motor-function-in-three-als-mouse-models
#19
Marion C Hogg, Luise Halang, Ina Woods, Karen S Coughlan, Jochen H M Prehn
BACKGROUND: Riluzole is the most widespread therapeutic for treatment of the progressive degenerative disease amyotrophic lateral sclerosis (ALS). Riluzole gained FDA approval in 1995 before the development of ALS mouse models. We assessed riluzole in three transgenic ALS mouse models: the SOD1G93A model, the TDP-43A315T model, and the recently developed FUS (1-359) model. METHODS: Age, sex and litter-matched mice were treated with riluzole (22 mg/kg) in drinking water or vehicle (DMSO) from symptom onset...
December 8, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/29196977/self-organized-cerebellar-tissue-from-human-pluripotent-stem-cells-and-disease-modeling-with-patient-derived-ipscs
#20
REVIEW
Keiko Muguruma
Recent advances in the techniques that differentiate induced pluripotent stem cells (iPSCs) into specific types of cells enabled us to establish in vitro cell-based models as a platform for drug discovery. iPSC-derived disease models are advantageous to generation of a large number of cells required for high-throughput screening. Furthermore, disease-relevant cells differentiated from patient-derived iPSCs are expected to recapitulate the disorder-specific pathogenesis and physiology in vitro. Such disease-relevant cells will be useful for developing effective therapies...
December 2, 2017: Cerebellum
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