Mode and site of action of therapies targeting CGRP signaling

Alejandro Labastida-Ramírez; Edoardo Caronna; Cédric Gollion; Emily Stanyer; Austeja Dapkute; Diana Braniste; Hoda Naghshineh; Liga Meksa; Nino Chkhitunidze; Tamari Gudadze; Patricia Pozo-Rosich; Rami Burstein; Jan Hoffmann

doi:10.1186/s10194-023-01644-8

Mode and site of action of therapies targeting CGRP signaling

J Headache Pain. 2023 Sep 11;24(1):125. doi: 10.1186/s10194-023-01644-8.

Authors

Alejandro Labastida-Ramírez¹, Edoardo Caronna^{2

3}, Cédric Gollion⁴, Emily Stanyer^{1

5}, Austeja Dapkute⁶, Diana Braniste^{7

8}, Hoda Naghshineh⁹, Liga Meksa¹⁰, Nino Chkhitunidze¹¹, Tamari Gudadze¹², Patricia Pozo-Rosich^{2

3}, Rami Burstein^{13

14

15}, Jan Hoffmann^{16

17}

Affiliations

¹ Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, SE1 1UL, UK.
² Headache Unit, Neurology Department, Vall d'Hebron Universitary Hospital, Barcelona, Spain.
³ Headache Research Group, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain.
⁴ Department of Neurology, University Hospital of Toulouse, Toulouse, France.
⁵ Nuffield Department of Clinical Neurosciences, Sleep and Circadian Neuroscience Institute, University of Oxford, Oxford, UK.
⁶ Centre of Neurology, Vilnius University, Vilnius, Lithuania.
⁷ Institute of Neurology and Neurosurgery, Diomid Gherman, Chișinău, Moldova.
⁸ State University of Medicine and Pharmacy, Nicolae Testemițanu, Moldova.
⁹ Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Science, Tehran, Iran.
¹⁰ Headache Unit, Neurology and Neurosurgery Department, Riga East University Hospital Gailezers, Riga, Latvia.
¹¹ Department of Neurology, Caucasus Medical Centre, Tbilisi, Georgia.
¹² Department of Neurology, Christian Hospital Unna, Unna, Germany.
¹³ Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁴ Department of Anesthesia, Harvard Medical School, Boston, MA, USA.
¹⁵ Center for Life Science, Room 649, 3 Blackfan Circle, Boston, MA, 02215, USA.
¹⁶ Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, SE1 1UL, UK. jan.hoffmann@kcl.ac.uk.
¹⁷ NIHR-Wellcome Trust King's Clinical Research Facility/SLaM Biomedical Research Centre, King's College Hospital, London, UK. jan.hoffmann@kcl.ac.uk.

Abstract

Targeting CGRP has proved to be efficacious, tolerable, and safe to treat migraine; however, many patients with migraine do not benefit from drugs that antagonize the CGRPergic system. Therefore, this review focuses on summarizing the general pharmacology of the different types of treatments currently available, which target directly or indirectly the CGRP receptor or its ligand. Moreover, the latest evidence regarding the selectivity and site of action of CGRP small molecule antagonists (gepants) and monoclonal antibodies is critically discussed. Finally, the reasons behind non-responders to anti-CGRP drugs and rationale for combining and/or switching between these therapies are addressed.

Keywords: Amylin; Anti-CGRP; Calcitonin; Headache; Migraine; Trigeminal.

Publication types

Review

MeSH terms

Antibodies, Monoclonal*
Calcitonin Gene-Related Peptide Receptor Antagonists / pharmacology
Calcitonin Gene-Related Peptide Receptor Antagonists / therapeutic use
Humans
Migraine Disorders* / drug therapy
Receptors, Calcitonin Gene-Related Peptide
Signal Transduction

Substances

Antibodies, Monoclonal
Calcitonin Gene-Related Peptide Receptor Antagonists
Receptors, Calcitonin Gene-Related Peptide