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anti-CGRP antibodies

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https://www.readbyqxmd.com/read/27909097/induction-of-migraine-like-photophobic-behavior-in-mice-by-both-peripheral-and-central-cgrp-mechanisms
#1
Bianca N Mason, Eric A Kaiser, Adisa Kuburas, Maria-Cristina M Loomis, John A Latham, Leon F Garcia-Martinez, Andrew F Russo
: The neuropeptide calcitonin gene-related peptide (CGRP) is a key player in migraine. While migraine can be treated using CGRP antagonists that act peripherally, the relevant sites of CGRP action remain unknown. To address the role of CGRP both within and outside the central nervous system, we used CGRP-induced light aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal, IP) injection of CGRP resulted in light aversive behavior in wild-type CD1 mice similar to aversion previously seen following central (intracerebroventricular, ICV) injection...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27899434/development-of-cgrp-dependent-pain-and-headache-related-behaviours-in-a-rat-model-of-concussion-implications-for-mechanisms-of-post-traumatic-headache
#2
Dara Bree, Dan Levy
BACKGROUND AND OBJECTIVE: Posttraumatic headache (PTH) is one of the most common, debilitating and difficult symptoms to manage after a mild traumatic brain injury, or concussion. However, the mechanisms underlying PTH remain elusive, in part due to the lack of a clinically relevant animal model. Here, we characterized for the first time, headache and pain-related behaviours in a rat model of concussion evoked by a mild closed head injury (mCHI) - the major type of military and civilian related trauma associated with PTH - and tested responses to current and novel headache therapies...
November 29, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27865545/anti-cgrp-antibodies-block-cgrp-induced-diarrhea-in-mice
#3
Eric A Kaiser, Brandon J Rea, Adisa Kuburas, Brian R Kovacevich, Leon F Garcia-Martinez, Ana Recober, Andrew F Russo
The multifunctional neuropeptide calcitonin gene-related peptide (CGRP) and its receptor are expressed throughout the gastrointestinal tract. Previous studies have shown that CGRP has roles in intestinal motility, water secretion, and inflammation. Furthermore, animal studies have demonstrated CGRP involvement in diarrhea secondary to C. difficile and food allergies. Diarrhea thus provides a convenient bioassay of CGRP activity in the GI system. In this proof of principle study, we report that prophylactic administration of an anti-CGRP antibody is able to block CGRP-induced diarrhea in mice...
November 14, 2016: Neuropeptides
https://www.readbyqxmd.com/read/27339365/anti-cgrp-monoclonal-antibodies-in-migraine-current-perspectives
#4
REVIEW
Maria Adele Giamberardino, Giannapia Affaitati, Martina Curto, Andrea Negro, Raffaele Costantini, Paolo Martelletti
Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration...
December 2016: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/27310178/chronic-migraine-treatment-from-onabotulinumtoxina-onwards
#5
Andrea Negro, Martina Curto, Luana Lionetto, Maria Adele Giamberardino, Paolo Martelletti
INTRODUCTION: WHO ranks migraine as the 6th highest cause of disability worldwide when considered alone, and the 3rd highest when medication overuse headache (MOH) is included. Migraine is an episodic disorder but in its natural course, its frequency could progressively increase and evolve to a chronic form. More than 50% of chronic migraine patients show acute pain medications overuse which is linked to the development of MOH. AREAS COVERED: Our goal is to review the existing data on OnabotulinoumtoxinA and CGRP-targeting drugs such as anti-CGRP monoclonal antibodies, one of the most promising migraine drugs under development...
October 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27206958/prevention-of-stress-or-nitric-oxide-donor-induced-medication-overuse-headache-by-a-calcitonin-gene-related-peptide-antibody-in-rodents
#6
Caroline Machado Kopruszinski, Jennifer Yanhua Xie, Nathan Mackenzie Eyde, Bethany Remeniuk, Sarah Walter, Jennifer Stratton, Marcelo Bigal, Juliana Geremias Chichorro, David Dodick, Frank Porreca
OBJECTIVE: The objective of this study was the determination of the role of calcitonin gene-related peptide (CGRP) in the induction of medication overuse headache (MOH)-related migraine in an injury-free preclinical model. METHODS: Rats were primed by a 7-day period of exposure to acute migraine therapies including sumatriptan and morphine. After an additional 14-day drug-free period, rats were exposed to putative migraine triggers including bright light stress (BLS) or nitric oxide (NO) donor in the presence or absence of TEV48125, a fully humanized CGRP antibody...
May 19, 2016: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/27194075/the-efficacy-of-nerve-growth-factor-antibody-in-a-mouse-model-of-neuropathic-cancer-pain
#7
Masayuki Miyagi, Tetsuhiro Ishikawa, Hiroto Kamoda, Miyako Suzuki, Gen Inoue, Yoshihiro Sakuma, Yasuhiro Oikawa, Kentaro Uchida, Takane Suzuki, Kazuhisa Takahashi, Masashi Takaso, Seiji Ohtori
Neuropathic cancer pain is caused by tumors compressing the spinal nerve roots and is usually difficult to treat. The aim of current study was to determine the influence of NGF antibody on pain-related markers and behavior in a mouse model of neuropathic cancer pain. Twenty mice were used to model neuropathic cancer pain by applying murine sarcoma cells to their left sciatic nerve. Ten mice were sham operated. Two weeks after surgery, the murine sarcoma-affected mice were allocated randomly into treatment groups receiving either sterile saline (saline group) or an anti-nerve growth factor antibody (anti-NGF group)...
November 1, 2016: Experimental Animals
https://www.readbyqxmd.com/read/26996577/efficacy-of-anti-nav1-7-antibody-on-the-sensory-nervous-system-in-a-rat-model-of-lumbar-intervertebral-disc-injury
#8
Daisuke Nojima, Kazuhide Inage, Yoshihiro Sakuma, Jun Sato, Sumihisa Orita, Kazuyo Yamauchi, Yawara Eguchi, Nobuyasu Ochiai, Kazuki Kuniyoshi, Yasuchika Aoki, Junichi Nakamura, Masayuki Miyagi, Miyako Suzuki, Gou Kubota, Takeshi Sainoh, Kazuki Fujimoto, Yasuhiro Shiga, Koki Abe, Hirohito Kanamoto, Gen Inoue, Kazuhisa Takahashi, Seiji Ohtori
PURPOSE: The pathophysiology of discogenic low back pain is not fully understood. Tetrodotoxin-sensitive voltage-gated sodium (NaV) channels are associated with primary sensory nerve transmission, and the NaV1.7 channel has emerged as an analgesic target. Previously, we found increased NaV1.7 expression in dorsal root ganglion (DRG) neurons innervating injured discs. This study aimed to examine the effect of blocking NaV1.7 on sensory nerves after disc injury. MATERIALS AND METHODS: Rat DRG neurons innervating the L5/6 disc were labeled with Fluoro-Gold (FG) neurotracer...
May 2016: Yonsei Medical Journal
https://www.readbyqxmd.com/read/26939344/-entity-of-acupoint-kinetic-changes-of-acupoints-in-histocytochemistry
#9
Wei He, Meiling Wu, Xiang-hong Jing, Wanzhu Bai, Bing Zhu, Xiaochun Yu
The present study aims to investigate the kinetic histocytochemical changes of acupoints in different condition. The expression of tryptase (+) mast cells, histamine (HA) , serotonin (5-HT) and nociceptive neuropeptides including calcitonin gene-related peptide (CGRP) and substance P (SP) were observed by immunohistochemistry combined with confocal technology. Mast cells were labeled with anti-mast cell tryptase antibody and simultaneously with HA or 5-HT primary antibodies to observe their co-expression. The results showed that: (1) SP and CGRP were expressed more highly on the cutaneous nerve fibers of "Hegu" (LI 4) after acupuncture stimulation than that of the control...
November 2015: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/26879279/safety-and-efficacy-of-amg-334-for-prevention-of-episodic-migraine-a-randomised-double-blind-placebo-controlled-phase-2-trial
#10
RANDOMIZED CONTROLLED TRIAL
Hong Sun, David W Dodick, Stephen Silberstein, Peter J Goadsby, Uwe Reuter, Messoud Ashina, Joel Saper, Roger Cady, Yun Chon, Julie Dietrich, Robert Lenz
BACKGROUND: The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18-60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system...
April 2016: Lancet Neurology
https://www.readbyqxmd.com/read/26653267/effect-of-administration-of-antibodies-against-nerve-growth-factor-in-a-rat-model-of-muscle-injury
#11
Masahiro Suzuki, Kazuhide Inage, Yoshihiro Sakuma, Sumihisa Orita, Kazuyo Yamauchi, Takane Suzuki, Miyako Suzuki, Go Kubota, Yasuhiro Oikawa, Takeshi Sainoh, Jun Sato, Kazuki Fujimoto, Yasuhiro Shiga, Koki Abe, Hirohito Kanamoto, Kazuhisa Takahashi, Seiji Ohtori
INTRODUCTION: Although muscle injury is a common source of pain, the mechanism causing such pain is not completely known. We have previously reported nerve growth factor (NGF) as a proinflammatory mediator involved in acute pain, and clinical trials have shown the effectiveness of anti-NGF antibodies for management of low back pain. Here, we aim to examine the effects of anti-NGF antibodies on muscle-derived pain by studying their effects on sensory innervation in a rat muscle injury model...
March 2016: Injury
https://www.readbyqxmd.com/read/26450103/isolation-of-potent-cgrp-neutralizing-antibodies-using-four-simple-assays
#12
Frances Neal, Joanne Arnold, Christine J Rossant, Sadhana Podichetty, David Lowne, Claire Dobson, Trevor Wilkinson, Caroline Colley, Rob Howes, Tristan J Vaughan
Calcitonin gene-related peptide (CGRP) is a small neuropeptide and a potent vasodilator that is widely associated with chronic pain and migraine. An antibody that inhibits CGRP function would be a potential therapeutic for treatment of these disorders. Here we describe the isolation of highly potent antibodies to CGRP from phage and ribosome display libraries and characterization of their epitope, species cross-reactivity, kinetics, and functional activity. Homogenous time-resolved fluorescence (HTRF) binding assays identified antibodies with the desired species cross-reactivity from naïve libraries, and HTRF epitope competition assays were used to characterize and group scFv by epitope...
January 2016: Journal of Biomolecular Screening
https://www.readbyqxmd.com/read/26432182/safety-tolerability-and-efficacy-of-tev-48125-for-preventive-treatment-of-high-frequency-episodic-migraine-a-multicentre-randomised-double-blind-placebo-controlled-phase-2b-study
#13
RANDOMIZED CONTROLLED TRIAL
Marcelo E Bigal, David W Dodick, Alan M Rapoport, Stephen D Silberstein, Yuju Ma, Ronghua Yang, Pippa S Loupe, Rami Burstein, Lawrence C Newman, Richard B Lipton
BACKGROUND: Calcitonin gene-related peptide (CGRP) is a validated target for the treatment of episodic migraine. Here we assess the safety, tolerability, and efficacy of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of high-frequency episodic migraine. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 2b study, we enrolled men and women (aged 18-65 years) from 62 sites in the USA who had migraine headaches 8-14 days per month...
November 2015: Lancet Neurology
https://www.readbyqxmd.com/read/26432181/safety-tolerability-and-efficacy-of-tev-48125-for-preventive-treatment-of-chronic-migraine-a-multicentre-randomised-double-blind-placebo-controlled-phase-2b-study
#14
RANDOMIZED CONTROLLED TRIAL
Marcelo E Bigal, Lars Edvinsson, Alan M Rapoport, Richard B Lipton, Egilius L H Spierings, Hans-Christoph Diener, Rami Burstein, Pippa S Loupe, Yuju Ma, Ronghua Yang, Stephen D Silberstein
BACKGROUND: Benefits of calcitonin-gene related peptide (CGRP) inhibition have not been established in chronic migraine. Here we assess the safety, tolerability, and efficacy of two doses of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of chronic migraine. METHODS: In this multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel-group phase 2b study, we enrolled men and women (aged 18-65 years) from 62 sites in the USA who had chronic migraine...
November 2015: Lancet Neurology
https://www.readbyqxmd.com/read/26148746/local-cutaneous-nerve-terminal-and-mast-cell-responses-to-manual-acupuncture-in-acupoint-li4-area-of-the-rats
#15
Mei-Ling Wu, Dong-Sheng Xu, Wan-Zhu Bai, Jing-Jing Cui, Hong-Ming Shu, Wei He, Xiao-Yu Wang, Hong Shi, Yang-Shuai Su, Ling Hu, Bing Zhu, Xiang-Hong Jing
Previous studies have shown that the effects of manual acupuncture (MA) are contributed by collagen fibers and mast cells in local acupoints, at which acupuncture stimulation causes various afferent fiber groups to be excited. However what happens in local nerve fibers and mast cells after MA remains unclear. The aim of this study was to examine the response of cutaneous nerve fibers and mast cells to MA stimulation in acupoint Hegu (LI4). The contralateral LI4 of the same rat was used as a non-stimulated control...
October 2015: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/26071945/anti-rankl-antibodies-decrease-cgrp-expression-in-dorsal-root-ganglion-neurons-innervating-injured-lumbar-intervertebral-discs-in-rats
#16
Masashi Sato, Kazuhide Inage, Yoshihiro Sakuma, Jun Sato, Sumihisa Orita, Kazuyo Yamauchi, Yawara Eguchi, Nobuyasu Ochiai, Kazuki Kuniyoshi, Yasuchika Aoki, Junichi Nakamura, Masayuki Miyagi, Miyako Suzuki, Gou Kubota, Takeshi Sainoh, Kazuki Fujimoto, Yasuhiro Shiga, Koki Abe, Hiroto Kanamoto, Gen Inoue, Kazuhisa Takahashi, Seiji Ohtori
PURPOSE: Nuclear factor-κB (NF-κB), receptor activator of NF-κB (RANK), and RANK ligand (RANKL) are transcriptional regulators of inflammatory cytokines. RANKL expression in dorsal root ganglion (DRG) neurons is elevated in animal models of pain or intervertebral disc herniation. We sought to evaluate the effect of anti-RANKL antibodies on sensory nerves innervating injured intervertebral discs. METHOD: We labeled DRG neurons innervating L5-6 discs with FluoroGold (FG)...
September 2015: European Spine Journal
https://www.readbyqxmd.com/read/26017524/emerging-treatments-for-the-primary-headache-disorders
#17
REVIEW
Nathaniel M Schuster, Sarah Vollbracht, Alan M Rapoport
Migraine and cluster headache are common, episodic, often chronic and disabling disorders of the brain. Although there are many standard treatment techniques, none are ideal. This article reviews various novel pharmacologic and device-related treatments for migraine and cluster headache. Emphasis is given to recent advances in the development of monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) and its receptor, including promising results from phase 2 trials studying the safety and efficacy of LY2951742, ALD403 and TEV-48125, three anti-CGRP mAbs...
May 2015: Neurological Sciences
https://www.readbyqxmd.com/read/25659293/development-of-a-fluorescent-immnunochromatographic-assay-for-the-procalcitonin-detection-of-clinical-patients-in-china
#18
Haiying Wang, Hong Wang, Shaopei Chen, Emmanuel E Dzakah, Keren Kang, Jihua Wang, Jufang Wang
BACKGROUND: Procalcitonin (PCT) has been recognized as a biomarker in severe inflammation, infection and sepsis. PCT detection in serum requires sensitive and specific antibodies. In this study, we generated monoclonal antibodies (mAbs) and developed fluorescent immunochromatographic assay for PCT detection. METHODS: Human recombinant PCT was used as immunogen. mAbs against PCT were developed and applied to fluorescent immunochromatographic assay for PCT detection in clinical samples...
April 15, 2015: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/25435318/the-therapeutic-armamentarium-in-migraine-is-quite-elderly
#19
EDITORIAL
Paolo Martelletti
Global Burden of Disease 2010 study considers migraine as one of the most important noncommunicable diseases in the world, classifying it third in terms of global prevalence (14.70%): it sums up the 54.19% of all the years of life lived with disabilities caused by the rest of all neurological disorders. This Editorial provides an historical excursus of old and new-entry molecules in migraine therapeutic area. Drugs for acute treatment such as triptans date back to the early 1990s with the appearance of sumatriptan and the following six triptans in the years immediately after (zolmitriptan, rizatriptan, naratriptan, eletriptan, almotriptan, frovatriptan)...
February 2015: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/25297013/safety-and-efficacy-of-ald403-an-antibody-to-calcitonin-gene-related-peptide-for-the-prevention-of-frequent-episodic-migraine-a-randomised-double-blind-placebo-controlled-exploratory-phase-2-trial
#20
RANDOMIZED CONTROLLED TRIAL
David W Dodick, Peter J Goadsby, Stephen D Silberstein, Richard B Lipton, Jes Olesen, Messoud Ashina, Kerri Wilks, David Kudrow, Robin Kroll, Bruce Kohrman, Robert Bargar, Joe Hirman, Jeff Smith
BACKGROUND: Calcitonin gene-related peptide (CGRP) is crucial in the pathophysiology of migraine. We assessed the safety, tolerability, and efficacy of ALD403, a genetically engineered humanised anti-CGRP antibody, for migraine prevention. METHODS: In this randomised, double-blind, placebo-controlled, exploratory, proof-of-concept phase 2 trial, patients aged 18-55 years with five to 14 migraine days per 28-day period were randomly assigned (1:1) via an interactive web response system to receive an intravenous dose of ALD403 1000 mg or placebo...
November 2014: Lancet Neurology
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