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Calcitonin gene-related peptide (CGRP), a neuropeptide abundant in the trigeminal system and widely expressed in both the peripheral and central nervous systems, has recently emerged as a promising target for migraine management. While known as a potent arterial vasodilator, the role of CGRP in migraine is likely mediated by modulating nociception and sustaining neurogenic inflammation that leads to further peripheral and central pain sensitization. Functional blockade of CGRP, which involves either CGRP receptor antagonists or monoclonal antibodies (mAbs) to CGRP or its receptor, has recently shown clinical efficacy in migraine management. The site of action, although still being studied, is likely in nervous system structures outside the blood-brain barrier. To date, four CGRP function-blocking mAbs (three target CGRP and one targets the CGRP receptor) are under clinical investigation for migraine prophylaxis. Phase II and III studies were promising with favorable safety profiles. CGRP function-blocking mAbs may potentially revolutionize the management of migraine. This review discusses in depth the fundamental role of CGRP in migraine pathogenesis as well as the clinical efficacy of CGRP function-blocking mAbs.
This article was published in the following journal.
Name: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy
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...
The benefit reported in a variety of clinical trials by a series of small molecule antagonists for the calcitonin gene-related peptide (CGRP) receptor, or four monoclonal antibodies against the neurop...
Calcitonin gene-related peptide (CGRP) has been reported as elevated in chronic migraine. We aimed to validate the role of interictal serum CGRP concentration in peripheral blood samples as a biomar...
Calcitonin gene related peptide (CGRP) is a mediator of neurogenic inflammation playing a major role in the pathogenesis of migraine. Increases in serum CGRP have been detected previously in migraineu...
Our previous survey on first-in-human trials (FIHT) of monoclonal antibodies (mAbs) showed that, due to their limited toxicity, the recommended phase II dose (RP2D) was only tentatively defined.
The investigators aim to investigate the incidence of migraine attacks after calcitonin gene-related peptide (CGRP) infusion in patients who have tried anti-CGRP monoclonal antibody treatm...
Amylin and calcitonin gene related peptide (CGRP) are related to the same peptide family. Both share 16 out of 37 amino acids and can activate each others receptor. CGRP is implicated in m...
The aim of the present study is to explore the importance of migraine phenotype on the headache/migraine responses after CGRP in FHM-patients, MA-patients and healthy volunteers.
The release of the neuropeptide calcitonin gene-related peptide (CGRP) is thought to play a causative role in migraine. Nociceptin immunoreactivity and ORL-1 mRNA have been detected in hum...
In patients known with migraine without aura a migraine headache or migraine like headache will be induced by infusion of calcitonin gene related peptide (CGRP). The patients will then be ...
Antibodies obtained from a single clone of cells grown in mice or rats.
Antibodies produced by clones of cells such as those isolated after hybridization of activated B LYMPHOCYTES with neoplastic cells. These hybrids are often referred to as HYBRIDOMAS.
Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab.
Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.
Cell surface proteins that bind calcitonin gene-related peptide (CGRP) with high affinity and trigger intracellular changes which influence the behavior of cells. CGRP receptors are present in both the central nervous system and the periphery and are not the same as calcitonin receptors.
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...