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anti-CGRP antibodies

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
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
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
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...
April 28, 2017: Lancet Neurology
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...
April 14, 2017: Clinical Pharmacology in Drug Development
Min Hou, Haiyan Xing, Yongqing Cai, Bin Li, Xianfeng Wang, Pan Li, Xiaolin Hu, Jianhong Chen
BACKGROUND: Migraine has been recognized as one of the leading causes of disability in the 2013 Global Burden of Disease Study and seriously affects the quality of patients' life, current treatment options are not ideal. Monoclonal antibodies to calcitonin gene-related peptide and its receptor (CGRP-mAbs) appear more promising for migraine because of considerably better effect and safety profiles. The objective of this study is to systematically assess the clinical efficacy and safety of CGRP-mAbs for migraine therapy...
December 2017: Journal of Headache and Pain
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. Although 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 CNS, we used CGRP-induced light-aversive behavior in mice as a measure of migraine-associated photophobia. Peripheral (intraperitoneal) injection of CGRP resulted in light-aversive behavior in wild-type CD1 mice similar to aversion seen previously after central (intracerebroventricular) injection...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
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
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
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
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
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 2017: Cephalalgia: An International Journal of Headache
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
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
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
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
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
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
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
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