Journal article
Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients
Annals of neurology, Vol.89(6), pp.1157-1171
03/27/2021
DOI: 10.1002/ana.26072
PMCID: PMC8486152
PMID: 33772845
Abstract
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).
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.
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.
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.
Details
- Title: Subtitle
- Amylin Analog Pramlintide Induces Migraine-like Attacks in Patients
- Creators
- Hashmat Ghanizada - Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, DenmarkBrandon J Rea - Department of Molecular Physiology and Biophysics, Center for the Prevention and Treatment of Visual Loss, Veterans Administration Health Center, Department of Neurology, University of Iowa, Iowa City, IAMohammad Al-Mahdi Al-Karagholi - Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, DenmarkLevi P Sowers - Department of Molecular Physiology and Biophysics, Center for the Prevention and Treatment of Visual Loss, Veterans Administration Health Center, Department of Neurology, University of Iowa, Iowa City, IAAndrew F Russo - Department of Molecular Physiology and Biophysics, Center for the Prevention and Treatment of Visual Loss, Veterans Administration Health Center, Department of Neurology, University of Iowa, Iowa City, IAChristopher S Walker - School of Biological Sciences and Centre for Brain Research, University of Auckland, Auckland, New ZealandNanna Arngrim - Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, DenmarkTayla Rees - School of Biological Sciences and Centre for Brain Research, University of Auckland, Auckland, New ZealandJakeb Petersen - School of Biological Sciences and Centre for Brain Research, University of Auckland, Auckland, New ZealandAndrew Siow - Maurice Wilkins Centre for Molecular Biodiscovery, School of Biological Sciences, University of Auckland, Auckland, New ZealandMette Mørch-Rasmussen - Department of Neurology, Danish Headache Center, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, DenmarkSheryl Tan - Department of Anatomy and Medical Imaging and Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Auckland, New ZealandSimon J O'Carroll - Department of Anatomy and Medical Imaging and Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Auckland, New ZealandPaul Harris - Maurice Wilkins Centre for Molecular Biodiscovery, School of Biological Sciences, University of Auckland, Auckland, New ZealandLene Theil Skovgaard - Department of Biostatistics, University of Copenhagen, Glostrup, DenmarkNiklas Rye Jørgensen - Department of Clinical Biochemistry, Rigshospitalet, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, DenmarkMargaret Brimble - Maurice Wilkins Centre for Molecular Biodiscovery, School of Biological Sciences, University of Auckland, Auckland, New ZealandJayme S Waite - Department of Molecular Physiology and Biophysics, Center for the Prevention and Treatment of Visual Loss, Veterans Administration Health Center, Department of Neurology, University of Iowa, Iowa City, IADebbie L Hay - Department of Pharmacology and Toxicology, University of Otago, Dunedin, New ZealandMessoud Ashina - Danish Headache Knowledge Center, Rigshospitalet Glostrup, Glostrup, Denmark
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.89(6), pp.1157-1171
- DOI
- 10.1002/ana.26072
- PMID
- 33772845
- PMCID
- PMC8486152
- NLM abbreviation
- Ann Neurol
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Publisher
- United States
- Grant note
- R155-2014-171 / Lundbeck Foundation R01 NS075599 / NINDS NIH HHS RF1 NS113839 / NINDS NIH HHS
- Language
- English
- Date published
- 03/27/2021
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Neurology (Pediatrics)
- Record Identifier
- 9984071699102771
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