Antigens and Antibodies in Disease With Specifics About CGRP Immunology

Taylor, Frederick R.

doi:10.1111/head.13409

Cited by 6 publications

(3 citation statements)

References 31 publications

(76 reference statements)

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“…Therefore, SNPs occurring along the CGRP receptor pathway could affect the clinical evolution of migraine and, thus, might influence to some extent the responsiveness to anti-CGRP(R) mAbs [ 20 ]. In particular, for mAbs directed towards CGRP and its receptor the affinity for the functional receptor effectors Fc receptors is fundamental for the maintenance of the antibody-ligand complex and for the mAb elimination half-life [ 27 ]. FcγRs are responsible for antibody-dependent cell-mediated cytotoxicity (ADCC) in cancer therapy [ 28 , 29 ], e.g.…”

Section: Introductionmentioning

confidence: 99%

Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy

et al. 2021

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Background the interest of clinical reaseach in polymorphisms and epigenetics in migraine has been growing over the years. Due to the new era of preventative migraine treatment opened by monoclonal antibodies (mAbs) targeting the signaling of the calcitonin-gene related peptide (CGRP), the present systematic review aims at identifying genetic variants occurring along the CGRP pathway and at verifying whether these can affect the clinical features and the course of disease and the responsiveness of patients to therapy. Methods the literature search has been conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science, the Human Genome Epidemiology (HuGE) Published Literature database (Public Health Genomics Knowledge Base) and Clinicaltrials.gov from database inception until April 1, 2021. The process of identification and selection of the studies included in the analysis has followed the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) criteria for systematic reviews and meta-analyses and the guidance from the Human Genome Epidemiology Network for reporting gene-disease associations. Results the search has retrieved 800 results, among which only 7 studies have met the eligibility criteria for inclusion in the analysis. The latter are case-control studies of genetic association and an exploratory analysis and two polymorphisms have been detected as the most recurring: the rs3781719 (T > C) of the CALC A gene encoding CGRP and the rs7590387 of the gene encoding the receptor activity-modifying protein (RAMP) 1 (C > G). Only one study assessing the methylation pattern with regard to CGRP pathway has been found from the search. No genetic association studies investigating the possible effect of genetic variants affecting CGRP signaling on the responsiveness to the most recent pharmacological approaches, i.e. anti-CGRP(R) mAbs, gepants and ditans, have been published. According to the Human Genome Epidemiology (HuGE) systematic reviews and meta-analyses risk-of-bias score for genetic association studies, the heterogeneity between and across studies and the small sample size do not allow to draw conclusions and prompt future studies. Conclusions adequately powered, good quality genetic association studies are needed to understand the impact of genetic variants affecting the pathway of CGRP on migraine susceptibility and clinical manifestation and to predict the response to therapy in terms of efficacy and safety.

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Section: Introductionmentioning

confidence: 99%

Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy

et al. 2021

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“…However, novel non-liver toxic gepants have now passed phase III (aterogepant, rimegepant, ubrogepant; see for review [15]). Antibodies against CGRP and the CGRP receptor are now approved for prevention in chronic migraine and in frequent episodic migraine [16], providing new prophylactic tools for migraine prevention.…”

Section: Introductionmentioning

confidence: 99%

The Presence of Calcitonin Gene-Related Peptide and Its Receptors in Rat, Pig and Human Brain: Species Differences in Calcitonin Gene-Related Peptide Pharmacology

et al. 2019

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Aim: The aim of present study is to investigate the binding characteristics of non-peptide calcitonin gene-related peptide (CGRP) receptor antagonists (i.e., gepants) in the brain membranes of rat, pig and human. Methods: The interaction of available gepants with the CGRP receptor was studied in the brain membranes of 3 different species using a radioligand competitive binding assay. In addition, the distribution of CGRP and its receptor component receptor activity modifying protein 1 (RAMP1) in rat cerebellum and cortex was explored using immunohistochemistry. Results: All gepants, except SB268262, displaced 100% of the radioligand specific binding in the brain tissue of all 3 species and showed highest affinity for CGRP receptors in human brain as compared to rat and pig brain membranes. Furthermore, radioligand binding studies revealed the presence of higher CGRP receptor density in human cerebellum compared to human cortex. The morphology, size and density of CGRP immunoreactive cells suggest that all cerebral cortical neurons were positive for CGRP. Slender receptor immunoreactive fibres were found spanning through the entire cortex. CGRP immunoreactivity was displayed in the cell soma of cerebellar Purkinje cells and in large neurons in the medial cerebellar nucleus. RAMP1 was found on the surface of the Purkinje cells and in parallel fibres, indicating presence in the granule cell axons. Conclusion: Cerebellum and cerebral cortex are rich in CGRP and CGRP receptors, which can be antagonized by gepants. However, all gepants display higher affinity for human CGRP receptors as compared to rat and pig CGRP receptors. Furthermore, human cerebellum seems to express higher density of CGRP receptors.

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“…10) mAbs targeting the CGRP pathway have advantages over small molecules because the mAbs have excellent specificity against the target, longer half-life, reduced potential for hepatotoxicity, and less potential for drug-drug interactions. 7,11) Erenumab, the only antibody targeting the CGRP receptor, is a fully human IgG2 mAb which binds to the receptor and blocks subsequent signaling. 6) CGRP is a key neurotransmitter in migraine pathogenesis.…”

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confidence: 99%

Systematic Review on the Efficacy and Safety of Erenumab for the Prevention of Migraine

Son

Chae

et al. 2019

Korean J Clin Pharm

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Migraine affects about 11% of the population worldwide and can be classified as either episodic or chronic on the basis of the number of migraine and headache days per month. 1) Episodic cases account for more than 90% of migraine patients and are defined as either headache or migraine occurring fewer than 15 days per month with or without aura. 2,3) Chronic migraine accounts for 5-8% of patients and is defined as 15 or more headache days per month for more than three months, of which at least 8 days are migraine with or without aura. 3,4) Currently, several options are available for the management of migraine such as pain-relievers and preventive medications. 5) Serotonin agonists (triptans) are the mainstay of pain-relievers (for acute management of migraine attacks) along with NSAIDs and acetaminophen while preventive medications consist of onabotulinum toxin A, antiseizure agents, antidepressants, and beta-blockers. 5) Recent progress regarding the pathogenesis of migraine, specifically via the calcitonin-gene-related peptide (CGRP)

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Antigens and Antibodies in Disease With Specifics About CGRP Immunology

Cited by 6 publications

References 31 publications

Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy

Role of CGRP pathway polymorphisms in migraine: a systematic review and impact on CGRP mAbs migraine therapy

The Presence of Calcitonin Gene-Related Peptide and Its Receptors in Rat, Pig and Human Brain: Species Differences in Calcitonin Gene-Related Peptide Pharmacology

Systematic Review on the Efficacy and Safety of Erenumab for the Prevention of Migraine

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