Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients.

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dc.contributor.author Ghanizada, Hashmat
dc.contributor.author Al-Karagholi, Mohammad Al-Mahdi
dc.contributor.author Walker, Christopher S
dc.contributor.author Arngrim, Nanna
dc.contributor.author Rees, Tayla
dc.contributor.author Petersen, Jakeb
dc.contributor.author Siow, Andrew
dc.contributor.author Mørch-Rasmussen, Mette
dc.contributor.author Tan, Sheryl
dc.contributor.author O'Carroll, Simon J
dc.contributor.author Harris, Paul
dc.contributor.author Skovgaard, Lene Theil
dc.contributor.author Jørgensen, Niklas Rye
dc.contributor.author Brimble, Margaret
dc.contributor.author Waite, Jayme S
dc.contributor.author Rea, Brandon J
dc.contributor.author Sowers, Levi P
dc.contributor.author Russo, Andrew F
dc.contributor.author Hay, Debbie L
dc.contributor.author Ashina, Messoud
dc.coverage.spatial United States
dc.date.accessioned 2022-06-22T02:50:52Z
dc.date.available 2022-06-22T02:50:52Z
dc.date.issued 2021-06
dc.identifier.citation (2021). Annals of Neurology, 89(6), 1157-1171.
dc.identifier.issn 0364-5134
dc.identifier.uri https://hdl.handle.net/2292/60085
dc.description.abstract <h4>Objective</h4>Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood, and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP).<h4>Methods</h4>Thirty-six migraine without aura patients were enrolled in a randomized, double-blind, 2-way, crossover, positive-controlled clinical trial study to receive infusion of an amylin analogue pramlintide or human αCGRP on 2 different experimental days. Furthermore, translational studies in cells and mouse models, and rat, mouse and human tissue samples were conducted.<h4>Results</h4>Thirty patients (88%) developed headache after pramlintide infusion, compared to 33 (97%) after CGRP (p = 0.375). Fourteen patients (41%) developed migraine-like attacks after pramlintide infusion, compared to 19 patients (56%) after CGRP (p = 0.180). The pramlintide-induced migraine-like attacks had similar clinical characteristics to those induced by CGRP. There were differences between treatments in vascular parameters. Human receptor pharmacology studies showed that an amylin receptor likely mediates these pramlintide-provoked effects, rather than the canonical CGRP receptor. Supporting this, preclinical experiments investigating symptoms associated with migraine showed that amylin treatment, like CGRP, caused cutaneous hypersensitivity and light aversion in mice.<h4>Interpretation</h4>Our findings propose amylin receptor agonism as a novel contributor to migraine pathogenesis. Greater therapeutic gains could therefore be made for migraine patients through dual amylin and CGRP receptor antagonism, rather than selectively targeting the canonical CGRP receptor. ANN NEUROL 2021;89:1157-1171.
dc.format.medium Print-Electronic
dc.language eng
dc.publisher Wiley
dc.relation.ispartofseries Annals of neurology
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm
dc.subject Trigeminal Ganglion
dc.subject Animals
dc.subject Mice, Inbred C57BL
dc.subject Humans
dc.subject Mice
dc.subject Rats
dc.subject Rats, Sprague-Dawley
dc.subject Calcitonin Gene-Related Peptide
dc.subject Cross-Over Studies
dc.subject Double-Blind Method
dc.subject Migraine Disorders
dc.subject Islet Amyloid Polypeptide
dc.subject Amylin Receptor Agonists
dc.subject Pain Research
dc.subject Neurosciences
dc.subject Chronic Pain
dc.subject Migraines
dc.subject Headaches
dc.subject Science & Technology
dc.subject Life Sciences & Biomedicine
dc.subject Clinical Neurology
dc.subject Neurosciences & Neurology
dc.subject 1103 Clinical Sciences
dc.subject 1109 Neurosciences
dc.title Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients.
dc.type Journal Article
dc.identifier.doi 10.1002/ana.26072
pubs.issue 6
pubs.begin-page 1157
pubs.volume 89
dc.date.updated 2022-05-02T22:26:17Z
dc.rights.holder Copyright: The author en
dc.identifier.pmid 33772845 (pubmed)
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/33772845
pubs.end-page 1171
pubs.publication-status Published
dc.rights.accessrights http://purl.org/eprint/accessRights/RetrictedAccess en
pubs.subtype Research Support, Non-U.S. Gov't
pubs.subtype Randomized Controlled Trial
pubs.subtype Journal Article
pubs.subtype Research Support, N.I.H., Extramural
pubs.elements-id 845386
pubs.org-id Medical and Health Sciences
pubs.org-id Science
pubs.org-id Chemistry
pubs.org-id Biological Sciences
pubs.org-id Science Research
pubs.org-id Medical Sciences
pubs.org-id Anatomy and Medical Imaging
pubs.org-id Maurice Wilkins Centre (2010-2014)
dc.identifier.eissn 1531-8249
pubs.record-created-at-source-date 2022-05-03
pubs.online-publication-date 2021-04-08


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