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anti-CGRP antibodies

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https://www.readbyqxmd.com/read/29878340/a-randomized-double-blind-placebo-controlled-study-to-evaluate-the-effect-of-erenumab-on-exercise-time-during-a-treadmill-test-in-patients-with-stable-angina
#1
Christophe Depre, Lubomir Antalik, Amaal Starling, Michael Koren, Osaro Eisele, Robert A Lenz, Daniel D Mikol
OBJECTIVE: To determine the potential impact of erenumab, a human anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody, on total exercise time (TET), time to exercise-induced angina, and ST depression in a double-blind, placebo-controlled study in patients with stable angina due to documented coronary artery disease. BACKGROUND: The relative importance of the CGRP receptor pathway during myocardial ischemia has not been established. METHODS: An exercise treadmill test was conducted following a single IV infusion of erenumab 140 mg or placebo...
May 2018: Headache
https://www.readbyqxmd.com/read/29848264/the-therapeutic-impact-of-new-migraine-discoveries
#2
Melinda Lukács, Janos Tajti, Ferenc Fülöp, Jozsef Toldi, Lars Edvinsson, Laszlo Vécsei
BACKGROUND: Migraine is one the most disabling neurological conditions and associates with high socio-economic costs. Though certain aspects of the pathomechanism of migraine are still incompletely understood, the leading hypothesis implicates the role of the activation of the trigeminovascular system. Triptans are considered the current gold standard therapy for migraine attacks; however, their use in clinical practice is limited. Prophylactic treatment includes non-specific approaches for migraine prevention...
May 29, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29719223/the-transient-receptor-potential-ankyrin-type-1-plays-a-critical-role-in-cortical-spreading-depression
#3
Liwen Jiang, Yan Wang, Yuewei Xu, Dongqing Ma, Minyan Wang
The transient receptor potential ankyrin type-1 (TRPA1) channels have been proposed as a potential target for migraine therapy. Yet the role of cortical TRPA1 channels in migraine mechanism has not been fully understood. Cortical spreading depression (CSD) is known as an underlying cause of migraine aura. The aim of this study is to investigate if cortical TRPA1 activity is required for CSD genesis and propagation. A mouse brain slice CSD model with intrinsic optical imaging was applied for TRPA1 signaling pharmacology...
April 29, 2018: Neuroscience
https://www.readbyqxmd.com/read/29623520/cgrp-monoclonal-antibodies-for-the-preventative-treatment-of-migraine
#4
REVIEW
Heike Israel, Lars Neeb, Uwe Reuter
PURPOSE OF REVIEW: CGRP is a key neuropeptide in migraine pathophysiology. The blockade of the CGRP pathway at the side of the CGRP receptor of the CGRP peptide leads to the interruption of trigeminal nerve system-mediated headache syndromes such as migraine. Monoclonal antibodies (mAbs) targeting the CGRP pathway have been developed and are currently under investigation for episodic (EM) and chronic migraine (CM) prevention. Here, we report data from these clinical trials. RECENT FINDINGS: Placebo-controlled, randomized double-blind phase studies of CGRP mAbs in episodic and chronic migraine have shown that the specific blockade of the peptide or the CGRP receptor are both powerful mechanisms to reduce migraine frequency...
April 6, 2018: Current Pain and Headache Reports
https://www.readbyqxmd.com/read/29616494/the-biology-of-monoclonal-antibodies-focus-on-calcitonin-gene-related-peptide-for-prophylactic-migraine-therapy
#5
REVIEW
Bianca Raffaelli, Uwe Reuter
Calcitonin gene-related peptide (CGRP) is 37-amino-acid neuropeptide, crucially involved in migraine pathophysiology. Four monoclonal antibodies (mAbs) targeting the CGRP pathway are currently under evaluation for the prevention of episodic and chronic migraine: eptinezumab (ALD403), fremanezumab (TEV-48125), galcanezumab (LY2951742), and erenumab (AMG334). As reviewed in this article, all 4 antibodies have been proven effective, tolerable, and safe as migraine prophylactic treatments in phase II clinical trials...
April 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29335794/effect-of-a-calcitonin-gene-related-peptide-binding-l-rna-aptamer-on-neuronal-activity-in-the-rat-spinal-trigeminal-nucleus
#6
Michael J M Fischer, Jakob Schmidt, Stanislav Koulchitsky, Sven Klussmann, Axel Vater, Karl Messlinger
BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a major role in the pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons integrate nociceptive afferent input from trigeminal tissues including intracranial afferents, and their activity is thought to reflect facial pain and headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have been demonstrated to be therapeutically effective in migraine. In parallel, CGRP receptor inhibition has been shown to lower spinal trigeminal neuron activity in animal models of meningeal nociception...
January 15, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29110503/cgrp-a-target-for-preventive-therapy-in-migraine-and-cluster-headache-systematic-review-of-clinical-data
#7
Sabrina Khan, Astrid Olesen, Messoud Ashina
Introduction Migraine and cluster headache are challenging to manage, with no tailored preventive medications available. Targeting the calcitonin gene-related peptide (CGRP) pathway to treat these headaches may be the first focused therapeutic option to date, with the potential for promising efficacy. Methods We systematically searched PubMed and clinicaltrials.gov for randomized controlled trials investigating the preventive potential of monoclonal antibodies against the CGRP pathway in the treatment of migraine and cluster headache...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29100502/efficacy-of-nerve-growth-factor-antibody-in-a-knee-osteoarthritis-pain-model-in-mice
#8
Masayuki Miyagi, Tetsuhiro Ishikawa, Hiroto Kamoda, Miyako Suzuki, Gen Inoue, Yoshihiro Sakuma, Yasuhiro Oikawa, Sumihisa Orita, Kentaro Uchida, Kazuhisa Takahashi, Masashi Takaso, Seiji Ohtori
BACKGROUND: Nerve growth factor (NGF) is not only an important factor in nerve growth but also a major contributor to the production of inflammation. It has been reported that inhibiting NGF could reduce several types of pain in several animal models. Here, we aimed to clarify the efficacy of NGF antibody in a knee osteoarthritis (OA) pain model in mice. METHOD: Six-week-old male C57BR/J mice were used (n = 30). Ten mice comprised the control group, which received saline injection into the right knee joints; the other 20 mice comprised the experimental group, which received monoiodoacetate (MIA) injection into the right knee joints...
November 3, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28972120/fremanezumab-a-humanized-monoclonal-anti-cgrp-antibody-inhibits-thinly-myelinated-a%C3%AE-but-not-unmyelinated-c-meningeal-nociceptors
#9
Agustin Melo-Carrillo, Andrew M Strassman, Rony-Reuven Nir, Aaron J Schain, Rodrigo Noseda, Jennifer Stratton, Rami Burstein
Calcitonin gene-related peptide (CGRP), the most abundant neuropeptide in primary afferent sensory neurons, is strongly implicated in the pathophysiology of migraine headache, but its role in migraine is still equivocal. As a new approach to migraine treatment, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs) were developed to reduce the availability of CGRP, and were found effective in reducing the frequency of chronic and episodic migraine. We recently tested the effect of fremanezumab (TEV-48125), a CGRP-mAb, on the activity of second-order trigeminovascular dorsal horn neurons that receive peripheral input from the cranial dura, and found a selective inhibition of high-threshold but not wide-dynamic range class of neurons...
November 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28942324/morphological-changes-in-different-populations-of-bladder-afferent-neurons-detected-by-herpes-simplex-virus-hsv-vectors-with-cell-type-specific-promoters-in-mice-with-spinal-cord-injury
#10
Nobutaka Shimizu, Mark F Doyal, William F Goins, Katsumi Kadekawa, Naoki Wada, Anthony J Kanai, William C de Groat, Akihide Hirayama, Hirotsugu Uemura, Joseph C Glorioso, Naoki Yoshimura
Functional and morphological changes in C-fiber bladder afferent pathways are reportedly involved in neurogenic detrusor overactivity (NDO) after spinal cord injury (SCI). This study examined the morphological changes in different populations of bladder afferent neurons after SCI using replication-defective herpes simplex virus (HSV) vectors encoding the mCherry reporter driven by neuronal cell-type-specific promoters. Spinal intact (SI) and SCI mice were injected into the bladder wall with HSV mCherry vectors driven by the cytomegalovirus (CMV) promoter, CGRP promoter, TRPV1 promoter or neurofilament 200 (NF200) promoter...
November 19, 2017: Neuroscience
https://www.readbyqxmd.com/read/28653227/anti-cgrp-monoclonal-antibodies-the-next-era-of-migraine-prevention
#11
REVIEW
Amy R Tso, Peter J Goadsby
Migraine is a very disabling disorder with severe impact on patients' lives and substantive costs to society in terms of healthcare costs and lost productivity. Prevention is a key component of migraine therapy, and while numerous preventive options exist, each is burdened by either troublesome side effects or insufficient efficacy. All migraine preventives currently in clinical use were licensed for other purposes and, by chance, have efficacy against migraine. As our understanding of migraine has evolved, calcitonin gene-related peptide (CGRP) has moved to the forefront as a neuropeptide central to migraine pathophysiology...
August 2017: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/28644160/calcitonin-gene-related-peptide-targeted-therapies-for-migraine-and-cluster-headache-a-review
#12
REVIEW
Nathaniel M Schuster, Alan M Rapoport
Calcitonin gene-related peptide (CGRP) is a signaling neuropeptide released from activated trigeminal sensory afferents in headache and facial pain disorders. There are a handful of CGRP-targeted therapies currently in phase 3 studies for migraine acute treatment or prevention. Currently, 4 monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab). Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine...
July 2017: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/28642283/selective-inhibition-of-trigeminovascular-neurons-by-fremanezumab-a-humanized-monoclonal-anti-cgrp-antibody
#13
Agustin Melo-Carrillo, Rodrigo Noseda, Rony-Reuven Nir, Aaron J Schain, Jennifer Stratton, Andrew M Strassman, Rami Burstein
A large body of evidence supports an important role for calcitonin gene-related peptide (CGRP) in migraine pathophysiology. This evidence gave rise to a global effort to develop a new generation of therapeutics that inhibit the interaction of CGRP with its receptor in migraineurs. Recently, a new class of such drugs, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs), were found to be effective in reducing the frequency of migraine. The purpose of this study was to better understand how the CGRP-mAb fremanezumab (TEV-48125) modulates meningeal sensory pathways...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28602628/overexpression-of-fibulin-5-attenuates-burn-induced-inflammation-via-trpv1-cgrp-pathway
#14
Xiaoqian Hou, Hui Li, Chunhua Zhang, Junling Wang, Xiuli Li, Xin Li
Fibulin-5, a multifunctional extracellular matrix protein, is up-regulated in response to mechanical injury and can promote dermal wound healing. This study aimed to explore the role and mechanism of Fibulin-5 in the pathogenesis of post-burn inflammation in thermally-injured mice. Here, we found that Fibulin-5 was up-regulated in the dorsal root ganglion (DRG) of burn-injured mice. After nociceptive behavioral testing, DRG was isolated and cultured to detect the mechanism of Fibulin-5 in thermal injury models by recombinant adenovirus overexpressing Fibulin-5, RT-qPCR, Western Blot, ELISA, AP20187 (an activator of one kind of kinase phosphorylating the α subunit of eukaryotic initiation factor 2, eIF2α), capsaicin (an agonist of transient receptor potential vanilloid (TRPV)-1), and an anti-CGRP neutralizing antibody...
August 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28565999/ryk-receptors-on-unmyelinated-nerve-fibers-mediate-excitatory-synaptic-transmission-and-ccl2-release-during-neuropathic-pain-induced-by-peripheral-nerve-injury
#15
Qing Ou Yang, Wen-Jing Yang, Jian Li, Fang-Ting Liu, Hongbin Yuan, Yue-Ping Ou Yang
Background Neuropathic pain is a major pathology of the central nervous system associated with neuroinflammation. Ryk (receptor-like tyrosine kinase) receptors act as repulsive axon-guidance molecules during development of central nervous system and neural injury. Increasing evidence suggests the potential involvement of Wnt/Ryk (wingless and Int) signaling in the pathogenesis of neuropathic pain. However, its underlying mechanism remains unknown. Results The expression and location of Ryk receptor as well as its ligand Wnt1 were detected by qPCR, Western blot, and immunohistochemistry...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28527063/the-role-of-anti-cgrp-antibodies-in-the-pathophysiology-of-primary-headaches
#16
REVIEW
Piero Barbanti, Cinzia Aurilia, Luisa Fofi, Gabriella Egeo, Patrizia Ferroni
Calcitonin gene-related peptide (CGRP), a potent vasodilator and pain-signaling neuropeptide, is a validated therapeutic target for migraine and cluster headache. Four anti-CGRP monoclonal antibodies (mAbs) have been developed, representing the first specific, mechanism-based, migraine prophylactic treatment. CGRP mAbs demonstrated good efficacy coupled to excellent tolerability and safety in 5 phase II clinical trials. Notably, CGRP mAbs induced complete migraine remission in a patients' subset. To date, more than 20 phase III trials using CGRP mAbs for of episodic and chronic migraine and cluster headache prevention are ongoing...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28497257/-therapy-of-migranes
#17
D Holle-Lee, S Nägel, C Gaul
In migraine attack treatment analgesics such as nonsteroidal anti-inflammatory drugs and triptans can be utilized. The efficacy of acute attack treatment is relevant to prevent migraine chronification. For prophylactic treatment β‑blockers, tricyclic antidepressants, flunarizine, antiepileptics and onabotulinumtoxin A are available. There is evidence that some other substances (e. g. sartans) are also efficacious in this regard. Furthermore, nondrug approaches are essential in migraine therapy. Early education and prophylactic treatment of patients at risk may prevent from medication overuse headache...
May 11, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28485848/the-trigeminovascular-pathway-role-of-cgrp-and-cgrp-receptors-in-migraine
#18
REVIEW
Lars Edvinsson
The trigeminal ganglion plays a key role in primary headache pathophysiology. Calcitonin gene-related peptide (CGRP) and CGRP receptors are expressed in trigeminal neurons that form C-fibers and A-fibers, respectively. In acute migraine and cluster headache attacks, there is release of CGRP into the cranial venous outflow. In addition, intravenous CGRP can induce migraine-like symptoms in migraine patients. These findings led to the development of anti-migraine therapies that inhibit CGRP action. Currently, CGRP receptor antagonists, the gepants, and monoclonal antibodies towards CGRP and the CGRP receptor are all showing positive relief of acute and chronic migraine in clinical trials...
May 2017: Headache
https://www.readbyqxmd.com/read/28460892/safety-and-efficacy-of-erenumab-for-preventive-treatment-of-chronic-migraine-a-randomised-double-blind-placebo-controlled-phase-2-trial
#19
RANDOMIZED CONTROLLED TRIAL
Stewart Tepper, Messoud Ashina, Uwe Reuter, Jan L Brandes, David Doležil, Stephen Silberstein, Paul Winner, Dean Leonardi, Daniel Mikol, Robert Lenz
BACKGROUND: The calcitonin gene-related peptide (CGRP) pathway is important in migraine pathophysiology. We assessed the efficacy and safety of erenumab, a fully human monoclonal antibody against the CGRP receptor, in patients with chronic migraine. METHODS: This was a phase 2, randomised, double-blind, placebo-controlled, multicentre study of erenumab for adults aged 18-65 years with chronic migraine, enrolled from 69 headache and clinical research centres in North America and Europe...
June 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28409893/spotlight-on-anti-cgrp-monoclonal-antibodies-in-migraine-the-clinical-evidence-to-date
#20
REVIEW
Lanfranco Pellesi, Simona Guerzoni, Luigi Alberto Pini
Migraine, a common neurovascular brain disorder, represents a severe and widespread health problem; along with medication-induced (medication-overuse) headache, it is the third-leading cause of disability worldwide. Currently, its therapeutic management remains unsatisfactory for several reasons; up to 40% of migraineurs are eligible for prophylactic treatment, but there are issues of efficacy, safety, and adherence. In recent years the evidence on the role of calcitonin gene-related peptide (CGRP) in migraine pathophysiology has been consolidated, so new and promising treatments for migraine pain and its possible prevention have been developed...
November 2017: Clinical Pharmacology in Drug Development
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