Journal ArticleDOI
CGRP as the target of new migraine therapies — successful translation from bench to clinic
Lars Edvinsson,Lars Edvinsson,Kristian Agmund Haanes,Karin Warfvinge,Karin Warfvinge,Diana N. Krause,Diana N. Krause +6 more
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Treatments that target calcitonin gene-related peptide (CGRP) and its receptor are proving effective for migraine treatment, and the hypothesis that CGRP has a major role in migraine pathophysiology is strongly supported.Abstract:
Treatment of migraine is on the cusp of a new era with the development of drugs that target the trigeminal sensory neuropeptide calcitonin gene-related peptide (CGRP) or its receptor. Several of these drugs are expected to receive approval for use in migraine headache in 2018 and 2019. CGRP-related therapies offer considerable improvements over existing drugs as they are the first to be designed specifically to act on the trigeminal pain system, they are more specific and they seem to have few or no adverse effects. CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. As these drugs come into clinical use, we provide an overview of knowledge that has led to successful development of these drugs. We describe the biology of CGRP signalling, summarize key clinical evidence for the role of CGRP in migraine headache, including the efficacy of CGRP-targeted treatment, and synthesize what is known about the role of CGRP in the trigeminovascular system. Finally, we consider how the latest findings provide new insight into the central role of the trigeminal ganglion in the pathophysiology of migraine.read more
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Development of therapeutic antibodies for the treatment of diseases
TL;DR: The preeminent antibody engineering technologies used in the development of therapeutic antibody drugs, such as humanization of monoclonal antibodies, phage display, the human antibody mouse, single B cell antibody technology, and affinity maturation are outlined.
Book
Physiology and pathophysiology
Wen-Quan Zou,Pierluigi Gambetti +1 more
TL;DR: The author examines the role of Cellular Prion Protein in the Amyloid-ss Oligomer Pathophysiology of Alzheimer's Disease, as well as modeling the Cell Biology of Prions and Yeast Prions.
Journal ArticleDOI
Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study.
Uwe Reuter,Peter J. Goadsby,Michel Lanteri-Minet,Shihua Wen,Peggy Hours-Zesiger,Michel D. Ferrari,Jan Klatt +6 more
TL;DR: Compared with placebo, erenumab was efficacious in patients with episodic migraine who previously did not respond to or tolerate between two and four previous migraine preventive treatments, and might be an option for patients with difficult-to-treat migraine who have high unmet needs and few treatment options.
Journal ArticleDOI
Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial.
Robert Croop,Peter J. Goadsby,Peter J. Goadsby,David A. Stock,Charles M. Conway,Micaela Forshaw,Elyse Stock,Vladimir Coric,Richard B. Lipton +8 more
TL;DR: In the acute treatment of migraine, a single 75 mg dose of rimegepant in an orally disintegrating tablet formulation was more effective than placebo and tolerability was similar to placebo.
Journal ArticleDOI
CGRP and the Trigeminal System in Migraine.
TL;DR: The goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene‐related peptide (CGRP) within the context of the trigeminovascular system.
References
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TL;DR: In this review the usual methods applied in systematic reviews and meta-analyses are outlined, and the most common procedures for combining studies with binary outcomes are described, illustrating how they can be done using Stata commands.
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Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
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Smith,Mari Smith,Badr Hasan Sobaih,Eugene Sobngwi,Reed J D Sorensen,Tatiane Cristina Moraes Sousa,Luciano A. Sposato,Chandrashekhar T Sreeramareddy,Vinay Srinivasan,Jeffrey D. Stanaway,Vasiliki Stathopoulou,Nicholas Steel,Murray B. Stein,Dan J. Stein,Dan J. Stein,Timothy J. Steiner,Timothy J. Steiner,Caitlyn Steiner,S. Steinke,S. Steinke,Mark A. Stokes,Lars Jacob Stovner,Bryan Strub,Michelle L Subart,Mu'awiyyah Babale Sufiyan,Bruno F. Sunguya,Bruno F. Sunguya,Patrick J Sur,Patrick J Sur,Soumya Swaminathan,Bryan L. Sykes,Dillon O Sylte,Rafael Tabarés-Seisdedos,Getachew Redae Taffere,Jukka Takala,Nikhil Tandon,Mohammad Tavakkoli,Nuno Taveira,Hugh R. Taylor,Arash Tehrani-Banihashemi,Tesfalidet Tekelab,Abdullah Sulieman Terkawi,Dawit Jember Tesfaye,Belay Tesssema,Ornwipa Thamsuwan,Katie E Thomas,Amanda G. Thrift,Tenaw Yimer Tiruye,Ruoyan Tobe-Gai,Mette Christophersen Tollånes,Mette Christophersen Tollånes,Marcello Tonelli,Roman Topor-Madry,Roman Topor-Madry,Miguel Tortajada,Mathilde Touvier,Bach Xuan Tran,Suryakant Tripathi,Christopher Troeger,Thomas Truelsen,Derrick Tsoi,Kald Beshir Tuem,Emin Murat Tuzcu,Stefanos Tyrovolas,Kingsley N. Ukwaja,Eduardo A. Undurraga,Eduardo A. Undurraga,Chigozie Jesse Uneke,Rachel L Updike,Olalekan A. Uthman,Benjamin S Chudi Uzochukwu,Job F M van Boven,Santosh Varughese,Tommi Vasankari,S Venkatesh,Narayanaswamy Venketasubramanian,Ramesh Vidavalur,Francesco Saverio Violante,Sergey K Vladimirov,Vasiliy Victorovich Vlassov,Stein Emil Vollset,Fiseha Wadilo,Tolassa Wakayo,Tolassa Wakayo,Yuan-Pang Wang,Marcia R. Weaver,Scott Weichenthal,Elisabete Weiderpass,Robert G. Weintraub,Andrea Werdecker,Ronny Westerman,Harvey Whiteford,Harvey Whiteford,Tissa Wijeratne,Charles Shey Wiysonge,Charles D.A. Wolfe,Charles D.A. Wolfe,Rachel Woodbrook,Anthony D. Woolf,Abdulhalik Workicho,Denis Xavier,Gelin Xu,Simon Yadgir,Mohsen Yaghoubi,Bereket Yakob,Lijing L Yan,Yuichiro Yano,Pengpeng Ye,Hassen Hamid Yimam,Paul S. F. Yip,Naohiro Yonemoto,Seok Jun Yoon,Marcel Yotebieng,Mustafa Z. Younis,Mustafa Z. Younis,Zoubida Zaidi,Maysaa El Sayed Zaki,Elias Asfaw Zegeye,Zerihun Menlkalew Zenebe,Xueying Zhang,Maigeng Zhou,Ben Zipkin,Sanjay Zodpey,Liesl Zühlke,Christopher J L Murray +778 more
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.
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The International Classification of Headache Disorders: 2nd edition
Journal ArticleDOI
RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.
Linda M. McLatchie,Neil J. Fraser,Martin J. Main,Alan Wise,Jason L. Brown,Nicola Thompson,Roberto Solari,Melanie G. Lee,Steven M. Foord +8 more
TL;DR: It is shown that a receptor with seven transmembrane domains, the calcitonin-receptor-like receptor (CRLR), can function as either a CGRP receptor or an adrenomedullin receptor, depending on which members of a new family of single-trans Membrane-domain proteins, which are called receptor-activity-modifying proteins or RAMPs, are expressed.
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Alternative RNA processing in calcitonin gene expression generates mRNAs encoding different polypeptide products
TL;DR: A model in which developmental regulation of RNA processing is used to increase the diversity of neuroendocrine gene expression is proposed.
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