ECNP Congress 2023 in Barcelona
Brain Prize Lecture by Peter Goadsby: Understanding migraine to develop novel therapeutics: A bench to bedside journey
Date: Tuesday 10 October, 10.05-10.50
Location: PL05
Peter Goadsby, United Kingdom
Brain Prize Winner 2021
Peter Goadsby FRS is director, NIHR King’s Clinical Research Facility, professor of neurology, King’s College London, an honorary consultant neurologist at King’s College Hospital and the Hospital for Sick Children, Great Ormond St, London, United Kingdom; and a National Institute for Health and Social Care Research senior investigator. He is professor emeritus of neurology, University of California, Los Angeles. His major research interests are in the basic mechanisms of primary headache disorders, such as migraine and cluster headache, in both experimental and clinical settings, and translating these insights into better management.
The world’s largest brain research prize is awarded annually by the Lundbeck Foundation. Each year, they award 10 million DKK (approx. 1,3 million EUR) to one or more neuroscientists who have made a ground-breaking impact on brain research. The Brain Prize was first awarded in 2011 and has so far honoured 38 scientists from 8 different countries
Outline:
The world's largest brain research prize is awarded by the Lundbeck Foundation. Each year, over 1 million Eur is awarded to one or more brain researchers who have had a ground-breaking impact on brain research.
Migraine is the most common cause of disability in those under the age of 50. Migraine is a pan-sensory disorder with canonical features of severe, often throbbing head pain that is aggravated by physical activity, and associated with sensitivity to light, sound and smells, and likely effects directly more than 1 billion worldwide. There is very often a premonitory stage before pain that can involved cognitive clouding, fatigue, somnolence, yawning, mood change, polyuria and food cravings (1).
Migraine involves activation, or the perception of activation, of trigeminal nociceptive afferents that innervate the dura mater. The second order synapse in the trigeminocervical complex in the caudal brainstem and upper cervical spinal cord employs glutamatergic and peptidergic transmission, including calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating polypeptide (PACAP). This synapse can be modulated by activation of serotonin 5-HT1B/1D receptor agonists, triptans. This scaffold is reproduced in at least the ventroposteromedial thalamus and periaqueductal grey (2).
Migraine therapeutics have been substantially improved in the last five years as the insights from the bench and from experimental medicine have been tested in randomized controlled trials. Monoclonal antibodies to CGRP, or to its canonical receptor, as well as small molecule CGRP receptor antagonists, gepants, have been developed. These medicines offer both preventive and acute treatment options that are effective and well tolerated (3). With yet further targets being explored, the promise of substantial reductions in disability is being realised as our understanding of the biology is exploited.
References
1. Ferrari MD, Goadsby PJ, Burstein R, Kurth T, Ayata C, Charles A, et al. Migraine. Nature Primers. 2022;8:2.
2. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S. Pathophysiology of Migraine- A disorder of sensory processing. Physiological Reviews. 2017;97:553-622.
3. Ashina M. Migraine. N Engl J Med. 2020;383:1866-76.