Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients.

Show simple item record Ghanizada, Hashmat Al-Karagholi, Mohammad Al-Mahdi Walker, Christopher S Arngrim, Nanna Rees, Tayla Petersen, Jakeb Siow, Andrew Mørch-Rasmussen, Mette Tan, Sheryl O'Carroll, Simon J Harris, Paul Skovgaard, Lene Theil Jørgensen, Niklas Rye Brimble, Margaret Waite, Jayme S Rea, Brandon J Sowers, Levi P Russo, Andrew F Hay, Debbie L Ashina, Messoud
dc.coverage.spatial United States 2022-06-22T02:50:52Z 2022-06-22T02:50:52Z 2021-06
dc.identifier.citation (2021). Annals of Neurology, 89(6), 1157-1171.
dc.identifier.issn 0364-5134
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.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 2022-05-02T22:26:17Z
dc.rights.holder Copyright: The author en
dc.identifier.pmid 33772845 (pubmed)
pubs.end-page 1171
pubs.publication-status Published
dc.rights.accessrights 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 Medical and Health Sciences Science Chemistry Biological Sciences Science Research Medical Sciences Anatomy and Medical Imaging Maurice Wilkins Centre (2010-2014)
dc.identifier.eissn 1531-8249
pubs.record-created-at-source-date 2022-05-03 2021-04-08

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